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Symposium Reports |
1 School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK
Abstract
All three forms of recombinant low voltage-activated T-type Ca2+ channels (Cav3.1, Cav3.2 and Cav3.3) exhibit a small, though clearly evident, window T-type Ca2+ current (ITwindow) which is also present in native channels from different neuronal types. In thalamocortical (TC) and nucleus reticularis thalami (NRT) neurones, and possibly in neocortical cells, an ITwindow-mediated bistability is the key cellular mechanism underlying the expression of the slow (< 1 Hz) sleep oscillation, one of the fundamental EEG rhythms of non-REM sleep. As the ITwindow-mediated bistability may also represent one of the cellular mechanisms underlying the expression of high frequency burst firing in awake conditions, ITwindow is of critical importance in neuronal population dynamics associated with different behavioural states.
(Received 28 September 2004;
accepted after revision 19 October 2004;
first published online 21 October 2004)
Corresponding author V. Crunelli: School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, UK. Email: crunelli{at}cardiff.ac.uk
Introduction
Low voltage-activated T-type Ca2+ channels are an important component of the large array of voltage-dependent membrane channels used by neurones to express different network dynamics. Their characteristic voltage dependence and kinetics allow them to generate a transient, depolarizing, low-threshold Ca2+ spike or potential (LTCP) which in turn evokes a peculiar firing pattern consisting of a high frequency (100–400 Hz) burst of action potentials (Huguenard, 1996; Perez-Reyes, 2003). Since the work of Llinas's group in Purkinje (Llinas & Sugimori, 1980a,b) and inferior olive neurones (Llinas & Yarom, 1981a,b), the physiological expression of neuronal T-type Ca2+ channels has now been demonstrated in different neurones and has become synonymous with LTCP generation and burst firing.
Recent work in thalamic neurones indicates that neuronal T-type Ca2+ channels also underlie membrane potential bistability, i.e. the existence of two resting membrane potentials. This neuronal property is due to the window current generated by these channels, i.e. ITwindow (Williams et al. 1997; Toth et al. 1998). Here, we summarize the biophysics underlying the physiological expression of ITwindow, and describe how the ITwindow-mediated bistability in thalamic neurones is a key component in the generation of the slow (< 1 Hz) sleep rhythm (Hughes et al. 2002), one of the fundamental EEG activities in non-REM sleep dynamics (Steriade et al. 1993d). In a prospective outlook we will then consider how neuronal ITwindow may underlie other activities during the awake state. The distinct and important physiological roles that ITwindow plays in non-neuronal cells have been reviewed elsewhere (Lambert et al. 2001; Perez-Reyes, 2003).
Biophysics of ITwindow
The window (or steady-state) component of an inactivating, voltage-dependent membrane current originates from the region of overlap (shaded in grey in Fig. 1Aa) between its steady-state activation and inactivation curves. In this voltage region, there is a fraction of channels which do not fully inactivate and therefore remain open. The estimated magnitude of the window current is strongly dependent on the steepness of these curves and their relative position with respect to the voltage axis (Fig. 1Aa). Since the activation and inactivation curves are obtained by fitting exponential functions to experimental measurements that in this voltage region are very small and highly dependent on the experimental conditions, great caution should be used in interpreting data on window currents. Furthermore, because these curves decay exponentially towards the voltage axis (i.e. they tend to zero at infinity) (Fig. 1Aa), all inactivating currents, including those with steady-state activation and inactivation curves that are far apart and shallow, possess a window current, even if extremely small. As has been the case for other inactivating currents, therefore, the issue is not whether neuronal ITwindow exists, but rather whether it has any physiological role, i.e. whether the small fraction of ‘non-inactivating’ neuronal T-type Ca2+ channels responsible for ITwindow makes any contribution to single neurone activities and neural network dynamics.
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1G, 1H and 1I pore forming subunits) have confirmed the results on native channels (Fig. 1Ba), and highlighted a larger ITwindow for Cav3.3 channels than for the other two types (Klockner et al. 1999) (Fig. 1Bb). These data are particularly important for thalamic cells, since glutamatergic thalamocortical (TC) neurones mostly express Cav3.1 and a very small number of Cav3.2 channels, whereas the GABAergic neurones of the nucleus reticularis thalami (NRT) are mainly endowed with Cav3.3 and much smaller amounts of Cav3.1 and Cav3.2 channels (Talley et al. 1999; Perez-Reyes, 2003). Neuronal ITwindow and membrane potential bistability
The transient activation of neuronal T-type Ca2+ channels generates the characteristic LTCP and associated high frequency burst firing. In contrast, the non-inactivating fraction of T-type Ca2+ channels leads, in the generally small membrane potential region of their expression, to a ‘steady’ influx of Ca2+ into the neurone, and thus to a ‘non-inactivating’ inward current (ITwindow) and a resulting ‘tonic’ depolarization. To fully appreciate the physiological significance of ITwindow in neuronal activity, however, it is necessary to consider the interaction between this current and the leak K+ current (Ileak) in the absence of other membrane currents. In Fig. 1Ab, the absolute amplitude of ITwindow (bell-shaped curve) has been plotted against the membrane potential, while two Ileaks are represented by the blue and green lines. When the slope of Ileak (i.e. gleak) is relatively small (green line in Fig. 1Ab), Ileak crosses the bell-shaped ITwindow curve in three points, at which both currents have equal values. Since ITwindow is an inward and Ileak an outward current, these are three points of zero net current (Fig. 1Ac): the leftmost and rightmost points are stable equilibrium points (filled and open circles on green line in Fig. 1Ac, respectively) whilst the middle point is unstable (i.e. grey circle in Fig. 1Ac). Under this condition the system generated by ITwindow and Ileak is bistable and, in the absence of other currents in this voltage region, neurones show two stable resting membrane potentials: one depolarized state where ITwindow is ‘on’ (open circle on green line in Fig. 1Ac) and a hyperpolarized state where ITwindow is ‘off’ (filled circle on green line in Fig. 1Ac). In contrast, when gleak is relatively large (blue line in Fig. 1Ab) Ileak crosses the ITwindow curve only in one point, which represents the resting membrane potential (filled circle on blue line in Fig. 1Ac).
Clearly, changes in Ileak are not the only modifications that can bring about or remove ITwindow-mediated bistability. As shown in Fig. 1Ad, bistability is lost when a small Ileak interacts with a small ITwindow, which may result either from a reduction in gT, rightward and leftward shifts in its steady-state activation and inactivation curve, respectively, or a decrease in their steepness. This would give rise to a single equilibrium point (filled circle on red line in Fig. 1Af). Also important, both from a biophysical and physiological perspective, are the cases where in the absence of any change in both ITwindow and Ileak, bistability can be instated or eliminated by addition of a tonic current (Fig. 1Ae). For example, in the non-bistable system of Fig. 1Ad, addition of a steady inward current (continuous purple line in Fig. 1Ae) would shift the entire net current–voltage curve downwards (continuous purple line in Fig. 1Af), thus reintroducing bistability. Addition of a larger steady inward current (dashed purple line in Fig. 1Ae) would then remove bistability, moving the curve even further downwards and thus allowing only one resting membrane potential to exist (open circle on dashed purple line in Fig. 1Af).
Physiological expression of ITwindow
Experimental confirmation of the presence of a physiologically relevant ITwindow has come from work in rat and cat TC neurones (Williams et al. 1997; Hughes et al. 1999; Hughes et al. 2002), of different sensory and motor thalamic nuclei (Blethyn et al. 2002), and NRT neurones (Blethyn et al. 2003). In these neurones bistability is observed after appropriate block of Ih (the most prominent current present within the voltage region where ITwindow is expressed), and, as predicted, appropriate voltage steps are able to switch the membrane potential between the two stable states (Williams et al. 1997) (Fig. 1C). This bistability is unaffected by Ba2+ and blockers of high threshold Ca2+ currents, including Cd2+, but is abolished by relatively small concentrations of Ni2+ (see Fig. 2D). The preferential block by Ni2+, compared to the lack of effect by similar concentrations of Cd2+, indicates that bistability is dependent on IT.
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ITwindow-mediated bistability is the cellular mechanism of the slow sleep (
1 Hz) oscillation
As shown by computer simulations, addition of the hyperpolarization-activated current (Ih) drastically transforms the ITwindow–Ileak bistable system into a continuous oscillation of the membrane potential (Fig. 2A), by introducing a voltage-dependent, non-inactivating inward current. The period, and other properties of this oscillation, are also critically controlled by the presence of a Ca2+-dependent, non-selective cation current (ICAN) (Hughes et al. 2002) (Fig. 2A).
This ITwindow-mediated, membrane potential oscillation is indeed the activity that is observed in TC and NRT neurones when Ih is not blocked (Fig. 2B). Extensive in vitro and in vivo studies (Hughes et al. 2002, 2004) have now shown it to represent the slow (< 1 Hz) sleep oscillation, i.e. the intracellularly recorded thalamic counterpart of the slow (< 1 Hz) sleep rhythm recorded in the EEG (Steriade et al. 1993a; Contreras & Steriade, 1995) (Fig. 2B). Both in animals (Steriade et al. 1993b) and in humans (Achermann & Borbely, 1997), this rhythm is one of the fundamental components of sleep dynamics during non-REM sleep, and a single slow (< 1 Hz) sleep oscillation cycle within the thalamocortical loop is now believed to underlie the expression of a K-complex in the EEG (Amzica & Steriade, 1997).
The bistability, and the slow (< 1 Hz) sleep oscillation, however, can be seen in vitro only in a very small proportion (15%) of TC neurones under control conditions (Williams et al. 1997), but in 56% of TC neurones following electrical stimulation of the cortical afferents present in the slice (Hughes et al. 2002). Similarly, none of the TC neurones in vivo expresses the slow (< 1 Hz) oscillation following removal of the cortex (a condition similar to the in vitro situation), but the majority shows it when the cortex is left intact (Timofeev & Steriade, 1996). Together these in vitro and in vivo results show that the corticofugal afferents to TC neurones strongly contribute to setting the ITwindow–Ileak system to become bistable, either by changing Ileak or ITwindow, or adding/removing a tonic input (as shown schematically in Fig. 1Ab, d and e, respectively). In TC neurones that are non-oscillating in control conditions in vitro, the simple addition of direct current does not bring about the slow (< 1 Hz) sleep oscillation, and an increase in gT or a modification of its voltage region of expression (by manipulating the relative position of the steady-state activation and inactivation curves of computer-generated IT) does not satisfactorily reproduce all the properties of the slow (< 1 Hz) oscillation (Hughes et al. 1999). On the other hand, dynamic clamp experiments that decrease Ileak show an oscillation with identical characteristics to the one observed in vivo (Hughes et al. 1999). Indeed, it is the synaptic activation of metabotropic glutamate receptors (mGluR1a) that instates the decrease in Ileak necessary for establishing the ITwindow–Ileak bistable system, as also demonstrated in vivo and in vitro using selective mGluR agonists and antagonists (Hughes et al. 2002, 2004) (Fig. 2C).
Figure 3 summarizes the cellular mechanism of the slow (< 1 Hz) sleep oscillation in TC neurones, where (i) ITwindow plays the major role by setting the level of the up (ITwindow ‘on’) and down (ITwindow ‘off’) states of the oscillation, (ii) Ih is responsible for repolarizing the neurone from the down state and thus critically determines the duration of the down state, and (iii) ICAN tightly controls the duration of the up state and is thus responsible for stabilizing the voltage region of existence of the slow oscillation (see Fig. 8 in Hughes et al. 2002). A very similar mechanism underlies the slow (< 1 Hz) sleep oscillation in NRT neurones (Fig. 2E), with ITwindow setting the basic levels for its up and down states (Blethyn et al. 2003).
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In the awake state, TC neurones are considerably more depolarized than during sleep, a situation similar to that depicted by the dashed purple line in Fig. 1Af where only one membrane potential exists (open circle) and bistability is not present. Computer simulations and in vitro experiments, however, have shown that even when the membrane potential of TC neurones is > –60 mV, a small EPSP (or IPSP) can temporarily bring the membrane potential into the voltage region where the ITwindow-mediated bistable mechanism could become transiently operational. This results in a stereotypical response consisting of a hyperpolarization (i.e. switching off of ITwindow) that is always terminated by an LTCP and associated high frequency burst firing (Fig. 4A and B), thus amplifying the output of TC neurones to small-amplitude, isolated, subthreshold synaptic potentials (Williams et al. 1997).
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Perspective outlook
The presence of Cav3.1, Cav3.2 and Cav3.3 channels in neurones of almost any brain region (Perez-Reyes, 2003) would support the notion that similar ITwindow-mediated activities as those described above for thalamic neurones may occur in various neuronal types throughout the brain. In particular, the ITwindow-mediated bistability might be the fundamental mechanism underlying the slow (< 1 Hz) sleep oscillation in neocortical cells (Steriade et al. 1993c), upon which synaptic influences would undoubtedly exert their modulation (Sanchez-Vives & McCormick, 2000).
Although we have concentrated here on the electrical behaviours that occur as a result of the ITwindow-mediated bistability, one should not discard the potential presence of other physiologically relevant effects of ITwindow that are specifically linked to Ca2+ influx, for example the modulation of biochemical pathways and gene expression. With the known role of intracellular Ca2+ in short- and long-term neuronal plasticity, these actions could be of particular significance for thalamic and cortical neurones in view of recent data on the effect of the deep stages of non-REM sleep on memory (Huber et al. 2004).
The discovery of a physiological role for ITwindow in thalamic neurones, and its likely involvement in the activities of many other neuronal types, clearly raise the question of potential alterations of this component of IT in neurological and psychiatric disorders. These could either be primary changes in IT that might contribute to pathophysiological conditions (Tsakiridou et al. 1995) or alterations in IT that are secondary to other abnormalities, such as extracellular pH changes (Shah et al. 2001), genetic mutations of other Ca2+ channels (Zhang et al. 2002), or continuous paroxysmal firing (Su et al. 2002).
Footnotes
In memory of Eberhard H. Buhl. This report was presented at The Journal of Physiology Symposium in honour of the late Eberhard H. Buhl on Structure/Function Correlates in Neurons and Networks, Leeds, UK, 10 September 2004. It was commissioned by the Editorial Board and reflects the views of the authors.
References
Achermann P & Borbely AA (1997). Low-frequency (< 1 Hz) oscillations in the human sleep electroencephalogram. Neuroscience 81, 213–222.[CrossRef][Medline]
Amzica F & Steriade M (1997). The K-complex: its slow (<1-Hz) rhythmicity and relation to delta waves. Neurology 49, 952–959.
Blethyn KL, Hughes SW, Cope DW & Crunelli V (2002). Nucleus-specific properties of the slow (<1 hz) oscillation in thalamic neurones in vitro. Soc Neurosci Abstr 28, 4.
Blethyn KL, Hughes SW, Cope DW & Crunelli V (2003). The role of ionic conductances underlying a slow (<1 hz) oscillation in neurones of the thalamic reticular nucleus in vitro. Soc Neurosci Abstr 29, 3.
Carbone E & Lux HD (1984). A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones. Nature 310, 501–502.[Medline]
Contreras D & Steriade M (1995). Cellular basis of EEG slow rhythms: a study of dynamic corticothalamic relationships. J Neurosci 15, 604–622.[Abstract]
Coulter DA, Huguenard JR & Prince DA (1989). Calcium currents in rat thalamocortical relay neurones: kinetic properties of the transient, low-threshold current. J Physiol 414, 587–604.
Crunelli V, Lightowler S & Pollard CE (1989). A T-type Ca2+ current underlies low-threshold Ca2+ potentials in cells of the cat and rat lateral geniculate nucleus. J Physiol 413, 543–561.
Destexhe A, Rudolph M, Fellous JM & Sejnowski TJ (2001). Fluctuating synaptic conductances recreate in vivo-like activity in neocortical neurons. Neuroscience 107, 13–24.[CrossRef][Medline]
Fanselow EE, Sameshima K, Baccala LA & Nicolelis MA (2001). Thalamic bursting in rats during different awake behavioral states. Proc Natl Acad Sci U S A 98, 15330–15335.
Fox AP, Nowycky MC & Tsien RW (1987). Single-channel recordings of three types of calcium channels in chick sensory neurones. J Physiol 394, 173–200.
Guido W & Weyand T (1995). Burst responses in thalamic relay cells of the awake behaving cat. J Neurophysiol 74, 1782–1786.
Hernandez-Cruz A & Pape HC (1989). Identification of two calcium currents in acutely dissociated neurons from the rat lateral geniculate nucleus. J Neurophysiol 61, 1270–1283.
Huber R, Ghilardi MF, Massimini M & Tononi G (2004). Local sleep and learning. Nature 430, 78–81.[CrossRef][Medline]
Hughes SW, Cope DW, Blethyn KL & Crunelli V (2002). Cellular mechanisms of the slow (<1 Hz) oscillation in thalamocortical neurons in vitro. Neuron 33, 947–958.[CrossRef][Medline]
Hughes SW, Cope DW, Toth TI, Williams SR & Crunelli V (1999). All thalamocortical neurones possess a T-type Ca2+ ‘window’ current that enables the expression of bistability-mediated activities. J Physiol 517, 805–815.
Hughes SW, Lorincz M, Cope DW, Blethyn KL, Kekesi KA, Parri HR et al. (2004). Synchronized oscillations at alpha and theta frequencies in the lateral geniculate nucleus. Neuron 42, 253–268.[CrossRef][Medline]
Huguenard JR (1996). Low-threshold calcium currents in central nervous system neurons. Annu Rev Physiol 58, 329–348.[CrossRef][Medline]
Klockner U, Lee JH, Cribbs LL, Daud A, Hescheler J, Pereverzev A et al. (1999). Comparison of the Ca2+ currents induced by expression of three cloned alpha1 subunits, alpha1G, alpha1H and alpha1I, of low-voltage-activated T-type Ca2+ channels. Eur J Neurosci 11, 4171–4178.[CrossRef][Medline]
Lambert RC, Leresche N, Kozlov AS, Hering J, Maulet Y, Richard S et al. (2001). Les entrées de calcium au voisinage du potentiel de repos: un rôle sur mesure pour les canaux T dans de multiples fonctions. Médicine/Science 17, 989–998.
Leresche N, Hering J & Lambert RC (2004). Paradoxical potentiation of neuronal T-type Ca2+ current by ATP at resting membrane potential. J Neurosci 24, 5592–5602.
Llinas R & Sugimori M (1980a). Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. J Physiol 305, 197–213.
Llinas R & Sugimori M (1980b). Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices. J Physiol 305, 171–195.
Llinas R & Yarom Y (1981a). Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage-dependent ionic conductances. J Physiol 315, 549–567.
Llinas R & Yarom Y (1981b). Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro. J Physiol 315, 569–584.
Massaux A & Edeline JM (2003). Bursts in the medial geniculate body: a comparison between anesthetized and unanesthetized states in guinea pig. Exp Brain Res 153, 573–578.[CrossRef][Medline]
McCormick DA (1992). Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity. Prog Neurobiol 39, 337–388.[CrossRef][Medline]
Nowycky MC, Fox AP & Tsien RW (1985). Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 316, 440–443.[CrossRef][Medline]
Perez-Reyes E (2003). Molecular physiology of low-voltage-activated T-type calcium channels. Physiol Rev 83, 117–161.
Ramcharan EJ, Gnadt JW & Sherman SM (2000). Burst and tonic firing in thalamic cells of unanesthetized, behaving monkeys. Vis Neurosci 17, 55–62.[CrossRef][Medline]
Sanchez-Vives MV & McCormick DA (2000). Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nat Neurosci 3, 1027–1034.[CrossRef][Medline]
Shah MJ, Meis S, Munsch T & Pape HC (2001). Modulation by extracellular pH of low- and high-voltage-activated calcium currents of rat thalamic relay neurons. J Neurophysiol 85, 1051–1058.
Sharp AA, O'Neil MB, Abbott LF & Marder E (1993). The dynamic clamp: artificial conductances in biological neurons. Trends Neurosci 16, 389–394.[CrossRef][Medline]
Sherman SM (2001). Tonic and burst firing: dual modes of thalamocortical relay. Trends Neurosci 24, 122–126.[CrossRef][Medline]
Steriade M, Contreras D, Curro Dossi R & Nunez A (1993a). The slow (< 1 Hz) oscillation in reticular thalamic and thalamocortical neurons: scenario of sleep rhythm generation in interacting thalamic and neocortical networks. J Neurosci 13, 3284–3299.[Abstract]
Steriade M, McCormick DA & Sejnowski TJ (1993b). Thalamocortical oscillations in the sleeping and aroused brain. Science 262, 679–685.
Steriade M, Nunez A & Amzica F (1993c). Intracellular analysis of relations between the slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram. J Neurosci 13, 3266–3283.[Abstract]
Steriade M, Nunez A & Amzica F (1993d). A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J Neurosci 13, 3252–3265.[Abstract]
Su H, Sochivko D, Becker A, Chen J, Jiang Y, Yaari Y et al. (2002). Upregulation of a T-type Ca2+ channel causes a long-lasting modification of neuronal firing mode after status epilepticus. J Neurosci 22, 3645–3655.
Swadlow HA & Gusev AG (2001). The impact of ‘bursting’ thalamic impulses at a neocortical synapse. Nat Neurosci 4, 402–408.[CrossRef][Medline]
Talley EM, Cribbs LL, Lee JH, Daud A, Perez-Reyes E & Bayliss DA (1999). Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels. J Neurosci 19, 1895–1911.
Timofeev I & Steriade M (1996). Low-frequency rhythms in the thalamus of intact-cortex and decorticated cats. J Neurophysiol 76, 4152–4168.
Toth TI, Hughes SW & Crunelli V (1998). Analysis and biophysical interpretation of bistable behaviour in thalamocortical neurons. Neuroscience 87, 519–523.[CrossRef][Medline]
Tsakiridou E, Bertollini L, de Curtis M, Avanzini G & Pape HC (1995). Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy. J Neurosci 15, 3110–3117.[Abstract]
Williams SR, Toth TI, Turner JP, Hughes SW & Crunelli V (1997). The ‘window’ component of the low threshold Ca2+ current produces input signal amplification and bistability in cat and rat thalamocortical neurones. J Physiol 505, 689–705.[CrossRef][Medline]
Zhang Y, Mori M, Burgess DL & Noebels JL (2002). Mutations in high-voltage-activated calcium channel genes stimulate low-voltage-activated currents in mouse thalamic relay neurons. J Neurosci 22, 6362–6371.
Acknowledgements
Work supported by the Wellcome Trust.
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