This study reports novel roles of the calcium-activated potassium channel of intermediate conductance, called IKCa, in pyramidal neurons of the CA1 region of the rat and mouse hippocampus. In addition to pharmacological profiling of the IKCa channel in these neurons, conducted using potent blockers of IKCa such as TRAM-34 and ChTx, single channels were found that fit the profile of IKCa including a potassium-selective single channel of ~30 pS conductance activated by calcium influx. In addition, the role of IKCa in generating the calcium-activated slow afterhyperpolarization (sAHP) was investigated. The molecular identity of the sAHP has eluded discovery for over 30 years despite it representing one of the strongest inhibitory responses in the brain. Here it is reported that IKCa channels generate a long-lasting, calcium-activated sAHP in response to bursts of synaptic activity and neuron firing, which is inhibited by TRAM-34. This work is important in identifying a novel ion channel in the brain and one of the primary contributors to the sAHP. These data will help to further our understanding of hippocampus-related phenomena, including behaviours such as spatial memory, with potential implications in other brain regions expressing IKCa channels.