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 Ca2+ during action potentials. Indeed, Ca2+-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 Ca2+) Ca2+ concentrations. Despite their low open probability under these conditions (V50 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 Ca2+ was a transient K+ (IA-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 Ca2+. Our results show that BK channels activate during action potentials and accelerate cell repolarisation even at minimal Ca2+ concentration, and suggest that they could do so also in the presence of extracellular Ca2+, before Ca2+ entering the cell facilitates their activity. © 2011 Springer-Verlag.