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

摘要

class="enumerated" style="list-style-type:decimal">Single channel recordings were performed on the cardiac calcium channel (α1C) in order to study the effect of coexpression of the accessory β2a subunit. On-cell patch clamp recordings were performed after expression of these channels in Xenopus oocytes.The α1C subunit, when expressed alone, had similar single channel properties to native cardiac channels. Slow transitions between low and high open probability (Po) gating modes were found as well as fast gating transitions between the open and closed states.Coexpression of the β2a subunit caused changes in the fast gating during high Po mode. In this mode, open time distributions reveal at least three open states and the β2a subunit favours the occupancy of the longest, 10-15 ms open state. No effect of the β2a subunit was found when the channel was gating in the low Po mode.Slow gating transitions were also affected by the β2a subunit. The high Po mode was maintained for the duration of the depolarizing pulse in the presence of the β2a subunit; while the α1C channel when expressed alone, frequently switched into and out of the high Po mode during the course of a sweep.The β2a subunit also affected mode switching that occurred between sweeps. Runs analysis revealed that the α1C 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.