Excitability of paraventricular nucleus neurones that project to the rostral ventrolateral medulla is regulated by small-conductance Ca2+-activated K+ channels.

Whole cell patch-clamp recordings were performed in brain slices to investigate mechanisms regulating the excitability of paraventricular nucleus (PVN) neurones that project directly to the rostral ventrolateral medulla (RVLM) (PVN-RVLM neurones) of rats. In voltage-clamp recordings, step depolarization elicited a calcium-dependent outward tail current that reversed near E(K). The current was nearly abolished by apamin and by UCL1684, suggesting mediation by small-conductance Ca(2+)-activated K(+) (SK) channels. In current-clamp recordings, depolarizing step current injections evoked action potentials that underwent spike-frequency adaptation (SFA). SK channel blockade with apamin or UCL1684 increased the spike frequency without changing the rate of SFA. Upon termination of step current injection, a prominent medium after-hyperpolarization potential (mAHP) was observed. SK channel blockade abolished the mAHP and revealed an after-depolarization potential (ADP). In response to ramp current injections, the rate of sub-threshold depolarization was increased during SK channel blockade, indicating that depolarizing input resistance was increased. Miniature EPSC frequency, amplitude, and decay kinetics were unaltered by bath application of apamin, suggesting that SK channel blockade likely increased excitability by a postsynaptic action. We conclude that although SK channels play little role in generating SFA in PVN-RVLM neurones, their activation nevertheless does dampen excitability. The mechanism appears to involve activation of a mAHP that opposes a prominent ADP that would otherwise facilitate firing.