BK Channel Modulation by the Gamma Subunit C-Terminal Peptides

Abstract

The large-conductance, Ca2+- and voltage-activated K+ (BK) channel consists of the pore-forming α subunits (BKα) and regulatory β and γ subunits. The γ1-3 subunits facilitate BK channel activation by shifting the voltage-dependence of channel activation toward hyperpolarization direction by approximately 50-150 mV. We previously showed that the C-termini of γ1 and γ3 contribute to the shift by ∼ 50 mV. In this study, we observed that the synthetic peptides of the γ1 and γ3 subunits’ C-terminal positively charged regions are able to shift the BKα channel's voltage-gating by ∼ 50 mV toward the hyperpolarization direction. Interestingly, the channel activating effect of the synthetic peptides was abolished by either the presence of a high concentration of Ca2+ or by charge neutralization mutation (5D→5N) of the Ca2+-bowl site. Similarly, the efficacy of the γ1 and γ3 subunit on BK channel modulation was also partially compromised in the presence of high Ca2+ or null Ca2+-bowl sites. We propose that the BK channel γ subunits modulate the channel's voltage gating in part via electrostatic interactions between their C-terminal positively charged regions and the BKα's Ca2+-bowl site.