Facilitation by the β(2a) subunit of pore openings in cardiac Ca2+ channels

Abstract

1. 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. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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.