Mr Scott Jones, Neuronal Integration Group, Eccles Institute of Neuroscience, JCSMR, ANU.
Small-conductance calcium-activated potassium channels, or SK channels, play an important role in regulating neuronal excitability. While SK channels at the soma have long been known to contribute to the medium after-hyperpolarization (mAHP), recent evidence indicates they also regulate NMDA receptor activation in dendritic spines. Here we investigate activation of SK channels in spines and dendrites of cortical pyramidal neurons during action potentials (APs), and compare this to activation of SK channels at the soma. Using confocal calcium imaging we demonstrate that inhibition of SK channels with apamin results in a location-dependent increase in calcium influx into dendritic spines during backpropagating APs (average increase ~30%). This effect was occluded by the R-type voltage-dependent calcium channel (VDCC) antagonist SNX482, but not by inhibition of spine calcium influx through N or P/Q type VDCCs or following block of calcium release from intracellular stores. During these experiments we noticed that the calcium indicator (Oregon Green BAPTA-1; 170-200 µM) completely blocked the apamin-sensitive mAHP at the soma, suggesting that somatic SK channels are not tightly co-localised with their calcium source. Consistent with this, we found that inhibition of P/Q, N, L and T type VDCCs, but not R-type VDCCs, reduced the amplitude of the mAHP. We conclude that SK channels in spines are activated solely by calcium influx through R-type VDCCs and therefore tightly coupled to this calcium source, whereas SK channels at the soma are activated by calcium influx through a variety of VDCCs indicating they are more weakly coupled to their calcium source.