Fig. 1

CCK-8 selectively decreased I_A. a, isolation of I_A in mouse DRG neurons. I_A was isolated by digital subtraction of current traces in which the transient outward K⁺ current had been inactivated by a brief delay at − 10 mV (100 ms, see Insets) from corresponding current traces without such a delay. This two-step voltage protocol was used for the isolation of I_A indicated in all subsequent experiments. b, effects of 5 mM 4-AP on the current density of I_A (n = 6). The current density was calculated as the ratio of peak current to membrane capacity (pA/pF). c, d time course of changes in I_A (c) or I_DR (d) peak amplitude mediated by 100 nM CCK-8. Insets show the exemplary current traces. The Arabic numerals indicate the relative points utilized for exemplary current traces. e, bar graph showing that 100 nM CCK-8 selectively decreased the current density of I_A indicated in panels B (n = 8) and C (n = 10) respectively. f a concentration-response curve for CCK-8 is displayed. Mean values on concentration-response curves were fitted to the sigmoidal Hill equation: PD ([CCK-8]) = PD_max/ (1 + (EC₅₀/[CCK-8])ⁿ), where PD_max is the maximal percent decrease of peak I_A, EC₅₀ is the concentration that produces half-maximum effect occurs and n is the Hill coefficient. Cell numbers at each concentration were shown in round brackets. g, h, CCK-8 did not significantly alter the steady-state activation curve of I_A (n = 9, g), but shifted the steady-state inactivation curve of I_A leftward (n = 12, f). i, summary data showing the effects of 100 nM CCK-8 on V_half of the activation and inactivation curves. Voltage-dependent activation was measured with voltage commands ranging from − 70 to + 70 mV (400 ms, in 10 mV increment). Steady-state voltage-dependent inactivation of I_A was determined by varying a 150-ms conditioning prepulse from − 120 to + 20 mV followed by a 500-ms voltage step pulse to + 40 mV. *p < 0.05, **p < 0.01 and ***p < 0.001 vs. control