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This Article Full Text Full Text (PDF) All Versions of this Article: 568/2/371    most recent jphysiol.2005.093161v1 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 Simeone, T. A Articles by Baram, T. Z Search for Related Content PubMed PubMed Citation Articles by Simeone, T. A Articles by Baram, T. Z

¹ Departments of Anatomy & Neurobiology and Pediatrics, University of California at Irvine, Irvine, CA, USA
² Barrow Neurological Institute and St Joseph's Hospital & Medical Center, Phoenix, AZ, USA

The hyperpolarization-activated cation current (I_h), mediated by HCN channels, contributes to intrinsic neuronal properties, synaptic integration and network rhythmicity. Recent studies have implicated HCN channels in neuropathological conditions including epilepsy. While native HCN channels have been studied at the macroscopic level, the biophysical characteristics of individual neuronal HCN channels have not been described. We characterize, for the first time, single HCN currents of excised inside-out patches from somata of acutely dissociated rat hippocampal CA1 pyramidal cells. Hyperpolarization steps elicited non-inactivating channel openings with an apparent conductance of 9.7 pS, consistent with recent reports of native and recombinant HCN channels. The voltage-dependent P_o had a V_1/2 of –81 ± 1.8 mV and slope –13.3 ± 1.9 mV. Blockers of macroscopic I_h, ZD7288 (50 µM) and CsCl (1 mM), reduced the channel conductance to 8 pS and 8.4 pS, respectively. ZD7288 was slightly more effective in reducing the P_o at depolarized potentials, whereas CsCl was more efficacious at hyperpolarized potentials. The unitary neuronal HCN channels had voltage-dependent latencies to first channel opening and two open states. As expected, ZD7288 and CsCl increased latencies and decreased the properties of both open states. The major endogenous positive modulator of macroscopic I_h is cAMP. Application of 8Br-cAMP (10 µM) did not affect conductance (9.4 pS), but did increase P_o and short and long open times. Thus, sensitivity to I_h modulators supports the single h-channel identity of these unitary currents. Detailed biophysical analysis of unitary I_h conductances is likely to help distinguish between homomeric and heteromeric expression of these channels – findings that may be relevant toward the pathophysiology of diseases such as epilepsy.

(Received 21 June 2005; accepted after revision 4 August 2005; first published online 25 August 2005)
Corresponding author T. Z. Baram: University of California, Irvine, Anatomy and Neurobiology, Med Sci I, Rm B-151, ZOT: 4475, Irvine, CA 92697, USA. Email: tallie{at}uci.edu

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