Calcium-activated K(+) channels of the K(Ca)2 type (SK channels) are prominently expressed in the mammalian brain, including hippocampus. These channels are thought to underlie neuronal excitability control and have been implicated in plasticity, memory, and neural disease. Contrary to previous reports, we found that somatic spike-evoked medium afterhyperpolarizations (mAHPs) and corresponding excitability control were not caused by SK channels but mainly by Kv7/KCNQ/M channels in CA1 hippocampal pyramidal neurons. Thus apparently, these SK channels are hardly activated by somatic Na(+) spikes. To further test this conclusion, we used sharp electrode, whole cell, and perforated-patch recordings from rat CA1 pyramidal neurons. We found that SK channel blockers consistently failed to suppress mAHPs under a range of experimental conditions: mAHPs following single spikes or spike trains, at -60 or -80 mV, at 20-30 degrees C, in low or elevated extracellular [K(+)], or spike trains triggered by synaptic stimulation after blocking N-methyl-d-aspartic acid receptors (NMDARs). Nevertheless, we found that SK channels in these cells were readily activated by artificially enhanced Ca(2+) spikes, and an SK channel opener (1-ethyl-2-benzimidazolinone) enhanced somatic AHPs following Na(+) spikes, thus reducing excitability. In contrast to CA1 pyramidal cells, bursting pyramidal cells in the subiculum showed a Na(+) spike-evoked mAHP that was reduced by apamin, indicating cell-type-dependent differences in mAHP mechanisms. Testing for other SK channel functions in CA1, we found that field excitatory postsynaptic potentials mediated by NMDARs were enhanced by apamin, supporting the idea that dendritic SK channels are activated by NMDAR-dependent calcium influx. We conclude that SK channels in rat CA1 pyramidal cells can be activated by NMDAR-mediated synaptic input and cause feedback regulation of synaptic efficacy but are normally not appreciably activated by somatic Na(+) spikes in this cell type.