title: Different calcium sources control somatic versus dendritic SK channel activation during action potentials.
abstract: Small-conductance calcium-activated potassium (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 afterhyperpolarization (mAHP), recent evidence indicates they also regulate NMDA receptor activation in dendritic spines. Here we investigate the activation of SK channels in spines and dendrites of rat cortical pyramidal neurons during action potentials (APs), and compare this to SK channel activation at the soma. Using confocal calcium imaging, we demonstrate that the inhibition of SK channels with apamin results in a location-dependent increase in calcium influx into dendrites and spines during backpropagating APs (average increase, ~40%). This effect was occluded by block of R-type voltage-dependent calcium channels (VDCCs), but not by inhibition of N- or P/Q-type VDCCs, or block of calcium release from intracellular stores. During these experiments, we noticed that the calcium indicator (Oregon Green BAPTA-1) blocked the mAHP. Subsequent experiments using low concentrations of EGTA (1 mm) produced the same result, suggesting that somatic SK channels are not tightly colocalized with their calcium source. Consistent with this idea, all known subtypes of VDCCs except R-type were calcium sources for the apamin-sensitive mAHP at the soma. We conclude that SK channels in spines and dendrites of cortical pyramidal neurons regulate calcium influx during backpropagating APs in a distance-dependent manner, and are tightly coupled to R-type VDCCs. In contrast, SK channels activated by APs at the soma of these neurons are weakly coupled to a variety of VDCCs.
authors: Eccles Institute of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra 0200, Australian Capital Territory, Australia.
authors: Scott L
authors: SL
authors: Jones
authors: Greg J
authors: GJ
authors: Stuart
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020908:Calcium Channels, R-Type / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D009930:Organic Chemicals / Q000494:pharmacology; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*
chemical_list: D020908:Calcium Channels, R-Type; C403124:Oregon Green BAPTA-dextran; D009930:Organic Chemicals; D051640:Small-Conductance Calcium-Activated Potassium Channels; D004533:Egtazic Acid; D002118:Calcium