title: Contribution of BK channels to action potential repolarisation at minimal cytosolic Ca2+ concentration in chromaffin cells.
abstract: BK channels modulate cell firing in excitable cells in a voltage-dependent manner regulated by fluctuations in free cytosolic Ca(2+) during action potentials. Indeed, Ca(2+)-independent BK channel activity has ordinarily been considered not relevant for the physiological behaviour of excitable cells. We employed the patch-clamp technique and selective BK channel blockers to record K(+) currents from bovine chromaffin cells at minimal intracellular (about 10 nM) and extracellular (free Ca(2+)) Ca(2+) concentrations. Despite their low open probability under these conditions (V(50) of +146.8 mV), BK channels were responsible for more than 25% of the total K(+) efflux during the first millisecond of a step depolarisation to +20 mV. Moreover, BK channels activated about 30% faster (τ = 0.55 ms) than the rest of available K(+) channels. The other main source of fast voltage-dependent K(+) efflux at such a low Ca(2+) was a transient K(+) (I(A)-type) current activating with V (50) = -14.2 mV. We also studied the activation of BK currents in response to action potential waveforms and their contribution to shaping action potentials both in the presence and the absence of extracellular Ca(2+). Our results show that BK channels activate during action potentials and accelerate cell repolarisation even at minimal Ca(2+) concentration, and suggest that they could do so also in the presence of extracellular Ca(2+), before Ca(2+) entering the cell facilitates their activity.
authors.affiliation: Departamento de Farmacología y Terapéutica, Universidad Autónoma de Madrid, 28029, Madrid, Spain.
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Scott
authors.forename: Diego
authors.initials: D
authors.lastname: Bustillo
authors.forename: Luis Alcides
authors.initials: LA
authors.lastname: Olivos-Oré
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Cuchillo-Ibañez
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Barahona
authors.forename: Emilio
authors.initials: E
authors.lastname: Carbone
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Artalejo
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*
chemical_list: D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; C048220:paxilline; C064719:iberiotoxin; D002118:Calcium