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. •CA1 pyramidal cells express intermediate conductance Ca2+-activated K+ channels (IKCa)•A slow AHP exhibits a pharmacological profile specific to IKCa channels•IKCa channels reduce temporal summation of EPSPs and mediate spike accommodation•IKCa channels are a key determinant of the slow AHP in CA1 pyramidal cells