Calcium influx via L- and N-type calcium channels activates a transient large-conductance Ca2+-activated K+ current in mouse neocortical pyramidal neurons.
Ca2+-activated K+ currents and their Ca2+ sources through high-threshold voltage-activated Ca2+ channels were studied using whole-cell patch-clamp recordings from freshly dissociated mouse neocortical pyramidal neurons. In the presence of 4-aminopyridine, depolarizing pulses evoked transient outward currents and several components of sustained currents in a subgroup of cells. The fast transient current and a component of the sustained currents were Ca2+ dependent and sensitive to charybdotoxin and iberiotoxin but not to apamin, suggesting that they were mediated by large-conductance Ca2+-activated K+ (BK) channels. Thus, mouse neocortical neurons contain both inactivating and noninactivating populations of BK channels. Blockade of either L-type Ca2+ channels by nifedipine or N-type Ca2+ channels by omega-conotoxin GVIA reduced the fast transient BK current. These data suggest that the transient BK current is activated by Ca2+ entry through both N- and L-type Ca2+ channels. The physiological role of the fast transient BK current was also examined using current-clamp techniques. Iberiotoxin broadened action potentials (APs), indicating a role of BK current in AP repolarization. Similarly, both the extracellular Ca2+ channel blocker Cd2+ and the intracellular Ca2+ chelator BAPTA blocked the transient component of the outward current and broadened APs in a subgroup of cells. Our results indicate that the outward current in pyramidal mouse neurons is composed of multiple components. A fast transient BK current is activated by Ca2+ entry through high-threshold voltage-activated Ca2+ channels (L- and N-type), and together with other voltage-gated K+ currents, this transient BK current plays a role in AP repolarization.
Sun
Xiaolu
X
Department of Pediatrics (Section of Respiratory Medicine), Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Gu
Xiang Q
XQ
Haddad
Gabriel G
GG
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D002469:Cell Separation; D018999:Charybdotoxin / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D019579:Neocortex / Q000166:cytology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051640:Small-Conductance Calcium-Activated Potassium Channels
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D002614:Chelating Agents; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D018999:Charybdotoxin; D001030:Apamin; C064719:iberiotoxin; D011188:Potassium; D002118:Calcium