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This Article Full Text Full Text (PDF) All Versions of this Article: 552/1/135    most recent jphysiol.2003.047191v1 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 Google Scholar Google Scholar Articles by Funahashi, M. Articles by Matsuo, R. Search for Related Content PubMed PubMed Citation Articles by Funahashi, M. Articles by Matsuo, R.

Role of the hyperpolarization-activated cation current (I_h) in pacemaker activity in area postrema neurons of rat brain slices

Makoto Funahashi, Yoshihiro Mitoh, Atsushi Kohjitani* and Ryuji Matsuo

To clarify the functional properties of the hyperpolarization-activated cation current (I_h) as a pacemaker current in area postrema neurons, whole-cell recordings were made in visually identified cells in rat brain slices. The activation of I_h was identified in approximately 62 % of area postrema neurons tested. The cells displaying I_h showed a depolarizing 'sag' in responses to hyperpolarizing current injection in current-clamp mode. The reversal potential for the I_h was -36 mV, and this was shown to depend on the external concentration of Na⁺ and K⁺ ions. Extracellular Cs⁺ ions (2 mM) and ZD7288 (100 µM), a potent selective I_h channel antagonist, blocked I_h and induced a membrane potential hyperpolarization, suggesting the sustained activation of I_h near the resting potential and a contribution from I_h to membrane potential maintenance at more depolarized levels. In contrast, extracellular Ba²⁺ ions caused a depolarization of the membrane potential, suggesting the blockade of inward rectifier K⁺ currents. ZD7288 decreased the spontaneous discharge rate by prolonging the slow depolarization between two spikes, with minimal effect on the amplitude of the afterhyperpolarization or action potential waveforms. I_h stabilized the latency of rebound action potentials. I_h was weakly activated by external 8-bromoadenosine 3',5' cyclic monophosphate (1 mM) or forskolin (50-100 µM), indicating that the I_h channel subtypes in area postrema cells could be modulated by intracellular cAMP. Our findings indicate that I_h contributes to the subthreshold membrane and firing properties of rat area postrema neurons and may regulate their resting membrane potential and firing patterns.