Facilitation by the β2a subunit of pore openings in cardiac Ca2+ channels

Abstract

Single channel recordings were performed on the cardiac calcium channel (α_1C) in order to study the effect of coexpression of the accessory β_2a subunit. On‐cell patch clamp recordings were performed after expression of these channels in Xenopus oocytes. The α_1C subunit, when expressed alone, had similar single channel properties to native cardiac channels. Slow transitions between low and high open probability (P_o) gating modes were found as well as fast gating transitions between the open and closed states. Coexpression of the β_2a subunit caused changes in the fast gating during high P_o mode. In this mode, open time distributions reveal at least three open states and the β_2a subunit favours the occupancy of the longest, 10‐15 ms open state. No effect of the β_2a subunit was found when the channel was gating in the low P_o mode. Slow gating transitions were also affected by the β_2a subunit. The high P_o mode was maintained for the duration of the depolarizing pulse in the presence of the β_2a subunit; while the α_1C channel when expressed alone, frequently switched into and out of the high P_o mode during the course of a sweep. The β_2a subunit also affected mode switching that occurred between sweeps. Runs analysis revealed that the α_1C subunit has a tendency toward non‐random mode switching. The β_2a subunit increased this tendency. A χ² analysis of contingency tables indicated that the β_2a subunit caused the α_1C channel to gain ‘intrinsic memory’, meaning that the mode of a given sweep can be non‐independent of the mode of the previous sweep. We conclude that the β_2a subunit causes changes to the α_1C channel in both its fast and slow gating behaviour. The β_2a subunit alters fast gating by facilitating movement of the channel into an existing open state. Additionally, the β_2a subunit decreases the slow switching between low and high P_o modes.