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

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 after-hyperpolarization 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.