IKCa Channels Are a Critical Determinant of the Slow AHP in CA1 Pyramidal Neurons

• CA1 pyramidal cells express intermediate-conductance Ca2+-activated K+ channels
• An sAHP 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 sAHP in CA1 pyramidal cells

SummaryControl 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 behavioral 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 behavioral or disease states associated with the sAHP.

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