IKCa channels are a critical determinant of the slow AHP in CA1 pyramidal neurons

Control over the frequency and pattern of neuronal spike discharge depends on Ca2+-gated K+channels that reduce cell excitability by hyperpolarizing the membrane potential. The Ca2+-dependent slow afterhyperpolarization (sAHP) is one of the most prominent inhibitory responses in the brain, with sAHP amplitude linked to a host of circuit and behavioural functions. Yet the channel that underlies the sAHP has defied identification for decades. Here we show that intermediate conductance Ca2+-dependent K+(IKCa) channels underlie the sAHP generated by trains of synaptic input or postsynaptic stimuli in CA1 hippocampal pyramidal cells. These findings are significant in providing a molecular identity for the sAHP of central neurons that will identify pharmacological tools capable of potentially modifying the several behavioural or disease states associated with the sAHP.