Figure 5.

Effect of GDP/GTP exchange on short-term desensitization. (A) Traces of simulated I_KACh elicited by 200 μM GTP. The bar above the current traces represents the period of GTP perfusion. To represent basal I_KACh activity in the corresponding experimental condition (11), 0.1 μM ACh was applied during the simulation period. I_KACh through the K_ACh/low channel only is shown as a dotted line. The arrowheads indicate the zero current level of each trace. The original values of initial [R_high] and [R_low] were used to represent high receptor expression in the experiments (11). (B) Effect of 1 mM GDP on I_KACh induced by 200 μM GTP. I_KACh was elicited in the same way as in A except that 1 mM GDP was applied during the entire simulation period. (C) Traces of simulated I_KACh elicited by 200 μM GTP with low receptor expression. I_KACh was elicited in the same way as in A except that [R_high] and [R_low] were lowered to 50% to represent low receptor expression in the experiments (11). (D) Effect of high GDP/GTP exchange activity on ACh-induced short-term desensitization. GDP/GTP exchange was enhanced by increasing the rate constants for GDP/GTP exchange (k_3,4 and k_-4,-3) by a factor of 5. The period during which ACh was perfused is shown as a bar above the current trace. (E) The effect of low GDP/GTP exchange activity on ACh-induced short-term desensitization. GDP/GTP exchange was lowered by reducing the rate constants to one-half.