Quinine blockade of currents through Ca2+-activated K+ channels in bovine chromaffin cells.

1. The blocking action of quinine of Ca2+-activated K+ channels was studied in excised inside-out patch recordings from cultured bovine chromaffin cells. Under normal ionic conditions (160 mM-K+ inside, 154 mM-Na+ outside), the unitary conductances measured between -20 and +40 mV were between 95 and 210 pS. 2. Quinine applied on the intracellular side of the membrane in micromolar concentrations chopped the unitary K+ currents into bursts of brief openings. These 'flickery bursts' appear to arise from discrete blocking and unblocking transitions. 3. Open and closed times within such flickery bursts were exponentially distributed suggesting a simple reaction between quinine and an open channel. 4. The blocking rate varied linearly with the concentration of quinine (rate coefficient 1.6 x 10(6) M-1 s-1). The unblocking rate was high (greater than 5000 s-1) and essentially independent of the quinine concentration. 5. The blocking rate was voltage dependent and increased with hyperpolarization which suggests that quinine acts predominantly or exclusively from the extracellular side of the membrane. The unblocking rate appeared to be independent of the membrane potential. 6. The probability of the open state was not altered by quinine indicating that quinine did not interfere directly with the gating process. 7. The total current carried by K+ ions was reduced by quinine only marginally (less than 10%) even at high quinine concentrations (1.5 mM). Moreover the reduction of the total current was also essentially voltage independent. 8. Quinine is clearly a very poor blocker. Poor block occurs, however, not only because of the brevity of the closed periods but presumably also because the channel can be closed only when it is not blocked. Only when the probability of channel opening (p) was high (greater than 0.85), i.e. when the channel's gate was predominantly open, did the flickery block appear to reduce the total current appreciably.