Figure 5.

The CCK depolarization is mediated through suppression of K_leak current. Representative current trace revealing the application of CCK8S elicits an inward current associated with a voltage-independent decrease in conductance. A: i. CCK8S (1.25 μM, 60 s) evokes inward current. The downward deflections are current responses to voltage ramps (−60 to −110 mV, 3 s in duration). ii. Expanded time base of responses to hyperpolarizing voltage ramps before CCK8S application (Pre-drug) and during the peak inward current (CCK8S) are shown. Each trace is an average of 5 sequential responses. After CCK8S application there is an inward shift of the holding current at V_hold = −60 mV, and a decrease in the slope of ramp response. The current responses intersect at approximately −94 mV. iii. CCK8S reduces a voltage-independent conductance that reverses near the potassium equilibrium potential. I_diff is the difference between the Pre-drug and CCK8S current responses in Aii plotted current vs. voltage. I_diff, which is attributable to the actions of CCK8S, has a linear slope, indicating a reduction in conductance. B: Intracellular cesium (Cs⁺) blocks the inward current evoked by CCK8S (1.25 μM, 60 s). i. Left, CCK8S evokes slow inward current in recording with K-gluconate electrode solution at holding potential of −60 mV. Right, Using cesium Cs⁺-gluconate pipette solution, CCK8S did not evoke inward current. ii. Population data illustrating the absence of the CCK8S-mediated inward current using the Cs⁺-containing pipette solution. All experiments were done in TTX.