Figure 4. CICR triggers BK channel-mediated transient outward currents.

(A) IbTX-sensitive transient outward currents. (Ai) In control, transient currents followed by sustained currents were evoked by depolarizing voltage steps (−30 to −10 mV from −70 mV holding potential, 10-mV increment). All transient current was inhibited by 100 nM IbTX (traces in IbTX and subtraction). IbTX-sensitive currents were obtained by subtracting traces in IbTX from control traces. (Aii) Summary of the peak current densities (left panel), and rise time and decay time constant of IbTX-sensitive currents (right panel). In (A) and (B), capacitive artifacts were blanked for clarity. Here and in following figures, dashed lines in current traces indicate zero current levels.

(B) RyRs are involved in the transient outward currents. Same voltage protocol as in (A). (Bi) Note that some transient outward currents remain in ryanodine (Bi, ryanodine). (Bii) Summary of peak current densities (left panel) and rise time and decay time constant of ryanodine-sensitive currents (right panel).

(Ci) Most of the transient current is suppressed by ω-Agatoxin-IVA (Aga-IVA, a P/Q-type blocker, 200 nM; trace in Aga-IVA and Aga-IVA-sensitive). Subsequent application of nonspecific Ca_v channel blockers (200 µM CdCl₂ and 500 µM NiCl₂) blocked transient currents almost completely (traces in lower panel in Ci). Data in (C) were recorded in the presence of TTX, synaptic blockers, and 1 mM 4-AP. (Cii) Summary of peak current densities (left panel), and the rise time and decay time constant of Aga-VIA-sensitive currents (right panel). (Ciii) Summary of effects of subtype-specific Ca_v blockers on transient currents. Aga-VIA inhibited transient currents more potently than nimodipine or TTA-P2. Effects are expressed as 100 × (selective blocker-sensitive current)/(nonspecific Ca_v blockers-sensitive current). ***p<0.001, unpaired t-test.