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

Abstract

To clarify the functional properties of the hyperpolarization-activated cation current (Ih) as a pacemaker current in area postrema neurons, whole-cell recordings were made in visually identified cells in rat brain slices. The activation of Ih was identified in approximately 62 % of area postrema neurons tested. The cells displaying Ih showed a depolarizing "sag" in responses to hyperpolarizing current injection in current-clamp mode. The reversal potential for the Ih 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 microM), a potent selective Ih channel antagonist, blocked Ih and induced a membrane potential hyperpolarization, suggesting the sustained activation of Ih near the resting potential and a contribution from Ih 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. Ih stabilized the latency of rebound action potentials. Ih was weakly activated by external 8-bromoadenosine 3',5' cyclic monophosphate (1 mM) or forskolin (50-100 microM), indicating that the Ih channel subtypes in area postrema cells could be modulated by intracellular cAMP. Our findings indicate that Ih contributes to the subthreshold membrane and firing properties of rat area postrema neurons and may regulate their resting membrane potential and firing patterns.