Distinct Ca²⁺ sources in dendritic spines of hippocampal CA1 Neurons Couple to SK and K_v4 Channels

Small conductance Ca²⁺-activated K⁺ (SK) channels and voltage-gated A-type K_v4 channels shape dendritic excitatory postsynaptic potentials (EPSPs) in hippocampal CA1 pyramidal neurons. Synaptically evoked Ca²⁺ influx through N-methyl-D-aspartate receptors (NMDARs) activates spine SK channels, reducing EPSPs and the associated spine head Ca²⁺ transient. However, results using glutamate uncaging implicated Ca²⁺ influx through SNX-482-sensitive (SNX-sensitive) Ca_v2.3 (R-type) Ca²⁺ channels as the Ca²⁺ source for SK channel activation. The present findings show that, using Schaffer collateral stimulation, the effects of SNX and apamin are not mutually exclusive and SNX increases EPSPs independent of SK channel activity. Dialysis with 1,2-bis(o-aminophenoxy)ethane-N'N'N'-tetraacetic acid (BAPTA), application of 4-Aminopyridine (4-AP), expression of a K_v4.2 dominant negative subunit, and dialysis with a KChIPs antibody occluded the SNX-induced increase of EPSPs. The results suggest two distinct Ca²⁺ signaling pathways within dendritic spines that link Ca²⁺ influx through NMDARs to SK channels and Ca²⁺ influx through R-type Ca²⁺ channels to K_v4.2-containing channels.