BK channel activation by brief depolarizations requires Ca²⁺ influx through L- and Q-type Ca²⁺ channels in rat chromaffin cells

Ca²⁺- and voltage-dependent BK-type K⁺ channels contribute to action potential repolarization in rat adrenal chromaffin cells. Here we characterize the Ca²⁺ currents expressed in these cells and identify the Ca²⁺ channel subtypes that gate the activation of BK channels during Ca²⁺ influx. Selective Ca²⁺ channel antagonists indicate the presence of at least four types of high-voltage-gated Ca²⁺ channels: L-, N-, P, and Q type. Mean amplitudes of the L-, N-, P-, and Q-type Ca²⁺ currents were 33, 21, 12, and 24% of the total Ca²⁺ current, respectively. Five-millisecond Ca²⁺ influx steps to 0 mV were employed to assay the contribution of Ca²⁺ influx through these Ca²⁺ channels to the activation of BK current. Blockade of L-type Ca²⁺ channels by 5 μM nifedipine or Q-type Ca²⁺ channels by 2 μM Aga IVA reduced BK current activation by 77 and 42%, respectively. In contrast, blockade of N-type Ca²⁺ channels by brief applications of 1-2 μM CnTC MVIIC or P-type Ca²⁺ channels by 50-100 nM Aga IVA reduced BK current activation by only 11 and 12%, respectively. Selective blockade of L- and Q-type Ca²⁺ channels also eliminated activation of BK current during action potentials, whereas almost no effects were seen by the selective blockade of N-or P-type Ca²⁺ channels. Finally, the L-type Ca²⁺ channel agonist Bay K 8644 promoted activation of BK current by brief Ca²⁺ influx steps by more than twofold. These data show that, despite the presence of at least four types of Ca²⁺ channels in rat chromaffin cells, BK channel activation in rat chromaffin cells is predominantly coupled to Ca²⁺ influx through L- and Q-type Ca²⁺ channels.