HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shao, Z. Articles by Yakel, J. L. Search for Related Content PubMed PubMed Citation Articles by Shao, Z. Articles by Yakel, J. L.

Single channel properties of neuronal nicotinic ACh receptors in stratum radiatum interneurons of rat hippocampal slices

Zuoyi Shao and Jerrel L. Yakel

MS 10855 Received 17 March 2000; accepted after revision 2 June 2000.

	ABSTRACT

Top Abstract Introduction Methods Results Discussion References

1. The single channel properties of neuronal nicotinic ACh receptors (nAChRs) were investigated in outside-out patches from CA1 stratum radiatum interneurons from thin slices of rat hippocampus.

2. The application of ACh (10 µM to 1 mM) induced the opening of observable single channel currents with two distinct current levels, which corresponded to conductance levels of 38 ± 3 and 62 ± 2 pS. The 38 pS channel was observed in 10 % (n = 260) of patches, whereas the 62 pS channel was observed in 4 % of patches; these two channel types were most often observed independently.

3. The 7-selective nAChR antagonist methyllycaconitine (MLA; 50 nM) reduced the open probability of the 38 pS channel by 73 %. In contrast, the 62 pS channel was unaffected by MLA, but instead was blocked by dihydro--erythroidine (DHE; 10 µM), a broad spectrum nAChR antagonist.

4. These data suggest that rat hippocampal CA1 stratum radiatum interneurons in the slice possess at least two different types of functional nAChRs, an 7-containing subtype with a single channel conductance of 38 pS, and a non-7 subtype with a single channel conductance of 62 pS.

	INTRODUCTION

Top Abstract Introduction Methods Results Discussion References

The neuronal nicotinic ACh receptor (nAChR) belongs to the superfamily of ligand-gated ion channels and is widely expressed throughout the nervous system where it participates in a variety of physiological processes including cognition, reward, development and analgesia (see review by Jones et al. 1999). Until recently the neuronal nAChR in the brain was thought to serve primarily a modulatory role as a presynaptic receptor to regulate neurotransmitter release from nerve terminals (McGehee & Role, 1995; Wonnacott, 1997). However, several recent reports have clearly demonstrated that nAChRs in the brain also function in a postsynaptic role by mediating fast cholinergic synaptic transmission (Roerig et al. 1997; Alkondon et al. 1998; Frazier et al. 1998a; Pettit & Yakel, 1999; but see McQuiston & Madison, 1999).

Currently at least 10 different nAChR subunits are known to be expressed in the rat CNS (McGehee & Role, 1995; McGehee, 1999). Until recently, neuronal nAChRs in the mammalian brain (and in particular the hippocampus) were thought to consist primarily of either heteromers of 42 subunits and possibly 34 subunits, or of homomers of the 7 subunit (Alkondon & Albuquerque, 1993; Zoli et al. 1998; Alkondon et al. 1999). However, it is becoming clear that there is much more diversity in the molecular makeup of neuronal nAChRs, and that other nAChR subunits are combining to form functional nAChRs, with different subtypes playing roles in different regions of the CNS (Alkondon & Albuquerque, 1993; Alkondon et al. 1997; Zoli et al. 1998; Jones et al. 1999; Léna et al. 1999; McGehee, 1999). In addition, whether 7-containing nAChRs are homomeric or heteromeric assemblies (i.e. combining with other nAChR subunits to form functional channels) in vivo still remains to be determined.

In many cases, the molecular makeup of nAChRs can be inferred from their functional properties (McGehee & Role, 1995). Therefore, we have investigated the properties of the single channel currents resulting from the activation of nAChRs in outside-out membrane patches from rat hippocampal CA1 stratum radiatum interneurons in the slice. We have found that ACh (10 µM to 1 mM) induced the opening of two distinct single channel types, one corresponding to a conductance level of 38 pS (observed in 10 % of 260 patches), and the other of 62 pS (4 % of patches). The pharmacological and physiological data presented here suggest that the 38 pS channel is an 7-containing nAChR that may include other non-7 subunits, and that the 62 pS channel is a non-7-containing receptor, thus further confirming the notion of the complex molecular subunit diversity of nAChR channels in the brain and hippocampus in vivo.

	METHODS

Top Abstract Introduction Methods Results Discussion References

Hippocampal slice preparation

Experiments were performed on rat hippocampal slices using procedures similar to those previously described (Jones & Yakel, 1997). Briefly, 1- to 3-week-old Wistar rats were anaesthetized with halothane and decapitated, and the brain was removed and placed into ice-cold artificial cerebrospinal fluid (ACSF; gassed with 95 % O₂ and 5 % CO₂) containing (mM): NaCl 126, KCl 3·5, CaCl₂ 2, MgCl₂ 6, NaH₂PO₄ 1·2, NaHCO₃ 25 and glucose 11; pH 7·4. Coronal sections of brain, which included the hippocampus, were cut into 350 µm slices using a Vibratome (Series 1000, Ted Pella, Inc., Redding, CA, USA). Slices were transferred to an incubation chamber containing experimental ACSF (with 1·3 mM MgCl₂ instead of 6 mM MgCl₂, gassed with 95 % O₂ and 5 % CO₂) at 30°C. All experiments were carried out in accordance with guidelines approved by the NIEHS Animal Care and Use Committee.

Single channel recordings

To study the single channel currents from outside-out membrane patches, patch pipettes were pulled from thick-walled borosilicate glass (catalogue no. B150-86-10; o.d. 1·5 mm, i.d. 0·86 mm; Sutter Instrument Co.) and had resistances of 5-10 M. The patch pipette filling solution contained (mM): caesium gluconate 140, MgCl₂ 2, CaCl₂ 0·5, Mg-ATP 2, BAPTA 5 and Hepes 10; and was adjusted to pH 7·2 with CsOH. Slices that had been incubated for at least 1 h were placed in the recording chamber and perfused with experimental ACSF at room temperature (18-22°C). Hippocampal CA1 stratum radiatum interneurons were visually identified by their location and morphology; outside-out patches were obtained from the soma of these cells. Single channel currents were obtained using an Axopatch 200B amplifier (Axon Instruments), lowpass filtered at 2-5 kHz and digitized at 10-20 kHz. All data were acquired with pCLAMP 7 software (Axon Instruments).

After excising patches, ACh (10 µM, unless otherwise specified) was applied (< 20 ms) to the patch via a synthetic quartz tube (i.d. 320 µm; Polymicro Technologies, Phoenix, AZ, USA) positioned 150-200 µm from the patch; the delivery of ACh was controlled by a computer-driven valve (General Valve, Fairfield, NJ, USA). As previously observed for central nAChR single channel currents in outside-out patches (Lester & Dani, 1994; Connolly et al. 1995), the activity of the channels tended to run down with time; single channel activity was usually gone after 10 min.

Single channel analysis

pCLAMP 7 software was used for the data analysis. Briefly, the average amplitudes of single channel currents were measured using all-points histograms that were fitted by Gaussian distributions. The accuracy of these amplitude values was confirmed by the measure, by hand, of individual longer duration events. The open probability and dwell times were estimated using Fetchan and pSTAT (pCLAMP 7 software, Axon Instruments). The detection of events was determined by the '50 % threshold' method. The dwell-time analysis was obtained from patches containing only a single channel, and was fitted by single or double exponential functions where appropriate. Differences between means were compared using one-way analysis of variance; P values of less than 0·05 were considered significantly different. All chemicals were obtained from Sigma except MLA, which was obtained from Research Biochemicals International.

	RESULTS

Top Abstract Introduction Methods Results Discussion References

ACh activates single channel currents with two distinct conductances

We obtained 260 outside-out patches from rat hippocampal CA1 stratum radiatum interneurons in the slice. The application of ACh (10 µM) to these patches induced the opening of two distinct (i.e. different current levels) and very brief single channel events (Fig. 1). At a holding potential of -60 mV, these two current levels were 2·3 and 3·7 pA, which corresponded to conductance levels of 38 ± 3 and 62 ± 2 pS, respectively. These two nAChR channel types were most often observed independently; the 38 pS channel was observed in 10 % of patches, whereas the 62 pS channel was observed in 4 % of patches. Only in two patches were both channel types observed. The single channel current-voltage (I-V ) relation for both channel types was linear for negative voltage ranges; no observed outward single channel events were ever observed at positive holding potentials, indicating strong inward rectification for both channel types (Fig. 1C and D).

		View larger version [in this window] [in a new window]
Figure 1. ACh induces the opening of two distinct single channel currents in rat hippocampal CA1 stratum radiatum interneurons A, the rapid application of ACh (10 µM) induced observable single channel currents at a holding potential (Vh) of -60 mV. Two distinct single channel current levels (a and b) co-existed in this patch. B, the amplitude histogram from the patch in A confirmed the existence of two populations of channels, with current levels of 2·3 and 3·7 pA. The current-voltage (I-V ) relation for the smaller (C) and larger (D) single channel currents from multiple patches are shown. The slope conductance, from the linear portion of the I-V plot at negative holding potentials (dashed line), averaged 38 ± 3 pS for the smaller conductance channel (C; n = 4), and 62 ± 2 pS for the larger conductance channel (D; n = 7). No outward current was seen at positive holding potentials for either channel type.

Characterization of the 38 pS channel

The 7-selective nAChR antagonist methyllycaconitine (MLA) was used to test whether the 38 pS channel contained the 7 nAChR subunit. MLA (50 nM) dramatically reduced the opening of the 38 pS channel (Fig. 2). For the patch shown in Fig. 2A, the application of ACh induced the opening of only the 38 pS channel (middle traces), and the subsequent addition of MLA blocked these channel events (right traces). In another patch, the open probability of the 38 pS channel was greatly reduced by MLA (by 84 %); the block by MLA was partly reversible after its removal (Fig. 2B). It should be noted that the lack of full reversibility is most probably due to the rundown of channel activity, which is often observed for central nAChR single channel currents in outside-out patches (Lester & Dani, 1994; Connolly et al. 1995). In four patches, MLA significantly reduced both the frequency of channel opening (by 58 %) and the open probability (by 73 %) as compared with control patches (8 patches; Fig. 2C); MLA had no effect on the amplitude of the single channel current (data not shown).

		View larger version [in this window] [in a new window]
Figure 2. Methyllycaconitine (MLA) blocks the 38 pS channel A, in the absence of agonist (left traces), no single channel events are seen at various holding potentials. The addition of ACh to this patch resulted in the opening of only the 38 pS channel (centre traces). The addition of MLA (50 nM) dramatically reduced the opening of this channel (right traces). B, in another patch, the open probability of the 38 pS channel (activated by 10 µM ACh) is plotted, with and without MLA; Vh = -60 mV. C, the frequency of channel opening (s-1; left) and the open probability (right) are both significantly decreased by MLA (* P < 0·05 and ** P < 0·01).

We analysed the open dwell times from patches containing the 38 pS channel before (8 patches) and during (4 patches) exposure to MLA; the open dwell time histograms were best fitted by a double exponential function (Fig. 3A). MLA significantly decreased the fast open dwell time by 43 % (from 0·23 ± 0·02 to 0·13 ± 0·03 ms); the slow open dwell time was not significantly altered by MLA (Fig. 3B). The quantification of these very brief open time values should be interpreted with caution in the context of the filter frequency (see Methods). The broad spectrum nAChR antagonist dihydro--erythroidine (DHE; 10 µM), which has a relatively low affinity for the 7 nAChR (Alkondon & Albuquerque, 1993; McQuiston & Madison, 1999), had no effect on the kinetics of the 38 pS channel (2 patches; data not shown). At a holding potential of -30 mV, the fast and slow open dwell times from patches (2) containing the 38 pS channel were 0·17 ± 0·01 and 1·6 ± 0·8 ms, respectively.

		View larger version [in this window] [in a new window]
Figure 3. Effect of MLA on open dwell times of the 38 pS channel The open dwell time distribution for control patches (n = 8) exposed to ACh (10 µM) containing only the 38 pS channel is shown in A, plotted as log time versus square root bin frequency (number of observations; Connolly et al. 1995); the histogram was best fitted by a double exponential function. The fast (fast) and slow (slow) time constant values are indicated on the figure; the ratio of the zero time intercepts of the fast and slow components was 5. B, MLA (50 nM; 4 patches) significantly decreased fast without affecting slow; * P < 0·05.

The activity of the 38 pS channel appeared to decrease in the continued presence of ACh, a process commonly referred to as desensitization. In 11 patches that were continually exposed to ACh (10 µM) and that contained only the 38 pS channel, the activity of the channel completely disappeared by 25 ± 10 s. Although it can be difficult to distinguish between desensitization and rundown, the kinetics of desensitization were in general more rapid and reversible.

Characterization of the 62 pS channel

MLA had no significant effect on the kinetics, the amplitude or the open probability of the 62 pS channel (Fig. 4A and B; 2 patches), suggesting that this type of nAChR does not contain the 7 nAChR subunit. However, DHE (10 µM) greatly reduced the open probability (2 patches) of the 62 pS channel (by 83 % for the patch shown; Fig. 4C and D); the block by DHE was mostly reversible after its removal (Fig. 4D). Like the 38 pS channel, the open time of the 62 pS channel was very brief. The open dwell time histogram (from 4 patches) was best fitted by a single exponential function with a time constant of 0·26 ± 0·1 ms.

		View larger version [in this window] [in a new window]
Figure 4. Pharmacology of the 62 pS channel A and B, MLA (50 nM) had no effect on the opening, amplitude or open probability of the 62 pS channel. C and D, dihydro--erythroidine (DHE; 10 µM) dramatically reduced the opening, and open probability, of the 62 pS channel. ACh (1 mM) was applied for 3 s (D; left), the bath solution was then washed out for 5 min, after which ACh and DHE were applied for 3 s (D; middle). After washing for 5 min, ACh was reapplied (D; right).

	DISCUSSION

Top Abstract Introduction Methods Results Discussion References

The activation of nAChRs in outside-out membrane patches from rat hippocampal CA1 stratum radiatum interneurons in the slice induced the opening of two distinct single channel conductance levels; the first had a conductance of 38 pS and contained the 7 nAChR subunit, and the second had a conductance of 62 pS and did not contain the 7 subunit. Both channel types strongly rectified (i.e. no outward current was ever observed at positive holding potentials), and had brief open time kinetics. Strong rectification of neuronal nAChR channels is often not observed in excised patches, perhaps due to the relief of spermine block (Connolly et al. 1995; Haghighi & Cooper, 1998); this suggests that the molecular makeup and/or the regulation of nAChRs in rat hippocampal interneurons may be different. These data are consistent with the previous functional identification from our laboratory and from others of the expression of diverse subtypes of nAChRs in rat hippocampal interneurons (see review by Jones et al. 1999).

The nAChRs are widely expressed throughout the CNS and are thought to be involved in a variety of different physiological and pathological conditions. One major issue concerning nAChRs in the brain is their molecular makeup. At least 10 different nAChR subunits are known to be expressed in the rat nervous system, and the properties of the channels are determined principally by the particular subunits that are forming channels. Pharmacological criteria have identified both 7 and non-7 subtypes as major components of the nAChRs in the rat hippocampal interneurons; however, the precise molecular identity of both the 7 and non-7 receptors remains to be determined (Jones et al. 1999).

Although native 7-containing nAChRs were initially conceived to be homomers of only the 7 subunits, much recent evidence suggests a marked diversity of native 7-containing nAChRs, strongly suggesting the possibility that other subunits may be combining with the 7 subunit in vivo (Girod et al. 1999). For example in chick sympathetic neurons, the 7 subunit contributes to the formation of at least three different types of native nAChRs, all of which are distinct from homomeric 7-containing receptors (Yu & Role, 1998a). Interestingly, both homomeric and heteromeric assemblies of 7-containing nAChRs, possibly involving the 5, 2 and/or 3 subunits, can be formed in Xenopus oocytes (Revah et al. 1991; Palma et al. 1999; Girod et al. 1999).

Therefore what might be the molecular 'identity' of the 38 pS channel that we have identified as the primary functional nAChR channel in patches excised from the soma of rat CA1 hippocampal stratum radiatum interneurons? One of the 7-containing 'heteromeric' nAChRs previously described in chick sympathetic neurons (Yu & Role, 1998a) has properties very similar to those of the 38 pS channel described here; it had a unitary conductance of 35 pS, was blocked by MLA, had a relatively brief mean open time and desensitized relatively slowly, all properties which differ from those of homomeric 7-containing nAChRs (Revah et al. 1991). Yu & Role (1998a) also found that the 7 subunit contributed to an 18 pS channel; this channel was blocked by -bungarotoxin (-BgTx), and appeared to also contain the 5 subunit (Yu & Role, 1998b). Therefore the 35 pS channel from chick sympathetic ganglia and the 38 pS channel from rat stratum radiatum interneurons are possibly similar 7-containing heteromeric nAChRs. Although for these receptors it appears as if the 7 subunit may not be combining with the 5 subunit, some indications suggest the possible involvement with a subunit. The 7 subunit has been reported to co-assemble with either the 2 or 3 subunits in Xenopus oocytes (Palma et al. 1999; Girod et al. 1999). In the accompanying paper (Sudweeks & Yakel, 2000), we have shown, using single-cell RT-PCR techniques in conjunction with whole-cell patch-clamp recordings, that these rat stratum radiatum interneurons co-express both the 7 and 2 subunits, and that both of the subunits are associated with fast-activating nAChR-mediated responses. Thus perhaps the 38 pS channel described here can be proposed to be an 72-containing receptor.

Determining the molecular identity of the 62 pS channel is even more elusive, in part due to its expected molecular heterogeneity and also to the low frequency of observing this channel in excised patches. It has been previously suggested that the major type of non-7 receptor in the hippocampus and other regions of the brain is composed of 42 subunits (Alkondon & Albuquerque, 1993; Zoli et al. 1998; Alkondon et al. 1999). However, the relatively large conductance value (i.e. 62 pS) that we have observed is much higher than that expected for 42 channels (Ramirez-Latorre et al. 1996). Recent work for both native nAChR channels in chick sympathetic neurons and expressed channels in Xenopus oocytes has demonstrated that the 5 nAChR subunit can form channels together with the 4 and 2 subunits, and that the conductance of these 5-containing channels is much larger (50 pS in the chick neurons) than for 42 channels (Ramirez-Latorre et al. 1996; Yu & Role, 1998b; Girod et al. 1999). The 5 subunit is also co-expressed along with the 4 and 2 subunits (and others) in these rat stratum radiatum interneurons (Sudweeks & Yakel, 2000) and in a subpopulation of neocortical interneurons (Porter et al. 1999), and all three of these subunits can be co-immunoprecipitated from chick brain (Conroy & Berg, 1998). Taken together, these data suggest the possibility that the molecular makeup of the 62 pS channel includes the 5, 4 and one or more subunits.

Previously Castro & Albuquerque (1993) reported that in cultured rat hippocampal neurons, nAChR activation induced the opening of a channel with a conductance of 73 pS, that had brief open time and desensitization kinetics, and that was blocked by MLA; thus this channel most probably contained the 7 nAChR subunit. Perhaps the reason why the properties of this 7-containing channel differed from those reported here for the 7-containing 38 pS channel in interneurons from rat hippocampal slices was that different experimental conditions were used. Cultured hippocampal neurons (presumably comprising mostly pyramidal neurons) are well known to express functional nAChRs (Zorumski et al. 1992; Alkondon & Albuquerque, 1993), whereas many investigators have reported that pyramidal neurons in slices have either no, or occasionally very small, nAChR-mediated responses (Alkondon et al. 1997; Jones & Yakel, 1997; Frazier et al. 1998b; McQuiston & Madison, 1999). As these pyramidal neurons in the slice express various nAChR subunits as detected using single-cell RT-PCR analysis (Sudweeks & Yakel, 2000), perhaps the expression of functional nAChRs is developmentally regulated and is altered under culture conditions. Interestingly single-channel recordings from thin slices from rat medial habenula also demonstrated multiple diverse types of nAChRs (Connolly et al. 1995).

In conclusion, our single channel data suggest that the two major types of functional nAChR channels in membrane patches excised from the soma of rat CA1 hippocampal stratum radiatum interneurons are an 7-containing receptor that may include other non-7 subunits, and another non-7-containing receptor that may include the 5 subunit. Thus from the data presented here and from several other labs, it is becoming clear that the in vivo subunit diversity of nAChR channels in the brain, and in the hippocampus in particular, is even much more complex than previously imagined.

	REFERENCES

Top Abstract Introduction Methods Results Discussion References

Alkondon, M. & Albuquerque, E. X. (1993). Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons. I. Pharmacological and functional evidence for distinct structural subtypes. Journal of Pharmacology and Experimental Therapeutics 265, 1455-1473	[Abstract]
Alkondon, M., Pereira, E. F. R. & Albuquerque, E. X. (1998). -bungarotoxin- and methyllycaconitine-sensitive nicotinic receptors mediate fast synaptic transmission in interneurons of rat hippocampal slices. Brain Research 810, 257-263	[Medline]
Alkondon, M., Pereira, E. F. R., Barbosa, C. T. F. & Albuquerque, E. X. (1997). Neuronal nicotinic acetylcholine receptor activation modulates -aminobutyric acid release from CA1 neurons of rat hippocampal slices. Journal of Pharmacology and Experimental Therapeutics 283, 1396-1411	[Abstract/Full Text]
Alkondon, M., Pereira, E. F. R., Eisenberg, H. M. & Albuquerque, E. X. (1999). Choline and selective antagonists identify two subtypes of nicotinic acetylcholine receptors that modulate GABA release from CA1 interneurons in rat hippocampal slices. Journal of Neuroscience 19, 2693-2705	[Abstract/Full Text]
Castro, N. G. & Albuquerque, E. X. (1993). Brief-lifetime, fast-inactivating ion channels account for the -bungarotoxin-sensitive nicotinic response in hippocampal neurons. Neuroscience Letters 164, 137-140	[Medline]
Connolly, J. G., Gibb, A. J. & Colquhoun, D. (1995). Heterogeneity of neuronal nicotinic acetylcholine receptors in thin slices of rat medial habenula. The Journal of Physiology 484, 87-105	[Abstract]
Conroy, W. G. & Berg, D. K. (1998). Nicotinic receptor subtypes in the developing chick brain: appearance of a species containing the 4, 2, and 5 gene products. Molecular Pharmacology 53, 392-401	[Abstract/Full Text]
Frazier, C. J., Buhler, A. V., Weiner, J. L. & Dunwiddie, T. V. (1998a). Synaptic potentials mediated via -bungarotoxin-sensitive nicotinic acetylcholine receptors in rat hippocampal interneurons. Journal of Neuroscience 18, 8228-8235	[Abstract/Full Text]
Frazier, C. J., Rollins, Y. D., Breese, C. R., Leonard, S., Freedman, R. & Dunwiddie, T. V. (1998b). Acetylcholine activates an -bungarotoxin-sensitive nicotinic current in rat hippocampal interneurons, but not pyramidal cells. Journal of Neuroscience 18, 1187-1195	[Abstract/Full Text]
Girod, R., Crabtree, G., Ernstrom, G., Ramirez-Latorre, J., McGehee, D., Turner, J. & Role, L. (1999). Heteromeric complexes of 5 and/or 7 subunits. Effects of calcium and potential role in nicotine-induced presynaptic facilitation. Annals of the New York Academy of Sciences 868, 578-590	[Medline]
Haghighi, A. P. & Cooper E. (1998). Neuronal nicotinic acetylcholine receptors are blocked by intracellular spermine in a voltage-dependent manner. Journal of Neuroscience 18, 4050-4062	[Abstract/Full Text]
Jones, S., Sudweeks, S. & Yakel, J. L. (1999). Nicotinic receptors in the brain: correlating physiology with function. Trends in Neurosciences 22, 555-561	[Medline]
Jones, S. & Yakel, J. L. (1997). Functional nicotinic ACh receptors on interneurones in the rat hippocampus. The Journal of Physiology 504, 603-610	[Abstract]
Léna, C., de Kerchove D'Exaerde, A., Cordero-Erausquin, M., Le Novere, N., del Mar Arroyo-Jimenez, M. & Changeux, J.-P. (1999). Diversity and distribution of nicotinic acetylcholine receptors in the locus ceruleus neurons. Proceedings of the National Academy of Sciences of the USA 96, 12126-12131	[Abstract/Full Text]
Lester, R. A. J. & Dani, J. A. (1994). Time-dependent changes in central nicotinic acetylcholine channel kinetics in excised patches. Neuropharmacology 33, 27-34	[Medline]
McGehee, D. S. (1999). Molecular diversity of neuronal nicotinic acetylcholine receptors. Annals of the New York Academy of Sciences 868, 565-577	[Medline]
McGehee, D. S. & Role, L. W. (1995). Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annual Review of Physiology 57, 521-546	[Medline]
McQuiston, A. R. & Madison, D. V. (1999). Nicotinic receptor activation excites distinct subtypes of interneurons in the rat hippocampus. Journal of Neuroscience 19, 2887-2896	[Abstract/Full Text]
Palma, E., Maggi, L., Barabino, B., Eusebi, F. & Ballivet, M. (1999). Nicotinic acetylcholine receptors assembled from the 7 and 3 subunits. Journal of Biological Chemistry 274, 18335-18340	[Abstract/Full Text]
Pettit, D. L. & Yakel, J. L. (1999). The differential distribution of postsynaptic nicotinic receptors. Society for Neuroscience Abstracts 25, 2259.
Porter, J. T., Cauli, B., Tsuzuki, K., Lambolez, B., Rossier, J. & Audinat, E. (1999). Selective excitation of subtypes of neocortical interneurons by nicotinic receptors. Journal of Neuroscience 19, 5228-5235	[Abstract/Full Text]
Ramirez-Latorre, J., Yu, C. R., Qu, X., Perin, F., Karlin, A. & Role, L. (1996). Functional contributions of 5 subunit to neuronal acetylcholine receptor channels. Nature 380, 347-351	[Medline]
Revah, F., Bertrand, D., Galzi, J.-L., Devillers-Thiéry, A., Mulle, C., Hussy, N., Bertrand, S., Ballivet, M. & Changeux, J.-P. (1991). Mutations in the channel domain alter desensitization of a neuronal nicotinic receptor. Nature 353, 846-849	[Medline]
Roerig, B., Nelson, D. A. & Katz, L. C. (1997). Fast synaptic signaling by nicotinic acetylcholine and serotonin 5-HT3 receptors in developing visual cortex. Journal of Neuroscience 17, 8353-8362	[Abstract/Full Text]
Sudweeks, S. & Yakel, J. L. (2000). Functional and molecular characterization of neuronal nicotinic ACh receptors in rat CA1 hippocampal neurones. The Journal of Physiology 527, 515-528.	[Abstract/Full Text]
Wonnacott, S. (1997). Presynaptic nicotinic ACh receptors. Trends in Neurosciences 20, 92-98	[Medline]
Yu, C. R. & Role, L. W. (1998a). Functional contribution of the 7 subunit to multiple subtypes of nicotinic receptors in embryonic chick sympathetic neurones. The Journal of Physiology 509, 651-665	[Abstract/Full Text]
Yu, C. R. & Role, L. W. (1998b). Functional contribution of the 5 subunit to neuronal nicotinic channels expressed by chick sympathetic ganglion neurones. The Journal of Physiology 509, 667-681	[Abstract/Full Text]
Zoli, M., Léna, C., Picciotto, M. R. & Changeux, J.-P. (1998). Identification of four classes of brain nicotinic receptors using 2 mutant mice. Journal of Neuroscience 18, 4461-4472	[Abstract/Full Text]
Zorumski, C. F., Thio, L. L., Isenberg, K. E. & Clifford, D. B. (1992). Nicotinic acetylcholine currents in cultured postnatal rat hippocampal neurons. Molecular Pharmacology 41, 931-936	[Abstract]

Acknowledgements

We would like to thank Drs David Armstrong and Christian Erxleben for critical reading of this manuscript. This work was supported by the NIEHS Intramural program.

Corresponding author

J. L. Yakel: NIEHS, 111 T.W. Alexander Drive, F2-08, PO Box 12233, Research Triangle Park, NC 27709, USA.

Email: yakel{at}niehs.nih.gov

This article has been cited by other articles:

				R. C. Klein and J. L. Yakel Functional somato-dendritic {alpha}7-containing nicotinic acetylcholine receptors in the rat basolateral amygdala complex J. Physiol., November 1, 2006; 576(3): 865 - 872. [Abstract] [Full Text] [PDF]

				D. Fayuk and J. L Yakel Ca2+ permeability of nicotinic acetylcholine receptors in rat hippocampal CA1 interneurones J. Physiol., August 1, 2005; 566(3): 759 - 768. [Abstract] [Full Text] [PDF]

				S. Ge and J. A. Dani Nicotinic Acetylcholine Receptors at Glutamate Synapses Facilitate Long-Term Depression or Potentiation J. Neurosci., June 29, 2005; 25(26): 6084 - 6091. [Abstract] [Full Text] [PDF]

				D. Fayuk and J. L. Yakel Regulation of Nicotinic Acetylcholine Receptor Channel Function by Acetylcholinesterase Inhibitors in Rat Hippocampal CA1 Interneurons Mol. Pharmacol., September 1, 2004; 66(3): 658 - 666. [Abstract] [Full Text] [PDF]

				W. Fu and J. H. Jhamandas {beta}-Amyloid Peptide Activates Non-{alpha}7 Nicotinic Acetylcholine Receptors in Rat Basal Forebrain Neurons J Neurophysiol, November 1, 2003; 90(5): 3130 - 3136. [Abstract] [Full Text] [PDF]

				L. Khiroug, R. Giniatullin, R. C. Klein, D. Fayuk, and J. L. Yakel Functional Mapping and Ca2+ Regulation of Nicotinic Acetylcholine Receptor Channels in Rat Hippocampal CA1 Neurons J. Neurosci., October 8, 2003; 23(27): 9024 - 9031. [Abstract] [Full Text] [PDF]

				M. Alkondon, E. F.R. Pereira, and E. X. Albuquerque NMDA and AMPA Receptors Contribute to the Nicotinic Cholinergic Excitation of CA1 Interneurons in the Rat Hippocampus J Neurophysiol, September 1, 2003; 90(3): 1613 - 1625. [Abstract] [Full Text] [PDF]

				S. Fucile, E. Palma, A. Martinez-Torres, R. Miledi, and F. Eusebi The single-channel properties of human acetylcholine alpha 7 receptors are altered by fusing alpha 7 to the green fluorescent protein PNAS, March 19, 2002; 99(6): 3956 - 3961. [Abstract] [Full Text] [PDF]

				R. Fabian-Fine, P. Skehel, M. L. Errington, H. A. Davies, E. Sher, M. G. Stewart, and A. Fine Ultrastructural Distribution of the {alpha}7 Nicotinic Acetylcholine Receptor Subunit in Rat Hippocampus J. Neurosci., October 15, 2001; 21(20): 7993 - 8003. [Abstract] [Full Text] [PDF]

				D. L. Pettit, Z. Shao, and J. L. Yakel {beta}-Amyloid1-42 Peptide Directly Modulates Nicotinic Receptors in the Rat Hippocampal Slice J. Neurosci., January 1, 2001; 21(1): RC120 - RC120. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shao, Z. Articles by Yakel, J. L. Search for Related Content PubMed PubMed Citation Articles by Shao, Z. Articles by Yakel, J. L.