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On the Mechanism of Inhibition of KATP Channels by Glibenclamide in Rat Ventricular Myocytes

Glibenclamide Block of KATP Channels. Introduction: The mechanism by which glibenclamide inhibits KATP channel activity has been examined in membrane patches from isolated rat ventricular cells. Methods and Results: Inside‐out patches were exposed to zero, or low, [ATP] to activate KATP channels. Glibenclamide did not affect single channel conductance, but reversibly reduced channel open probability from either side of the membrane. Internal (cytoplasmic) glibenclamide inhibited with half‐maximal inhibitory [glibenclamide] = 6 μM, Hill coefficient = 0.35. Complete channel inhibition was not observed, even at 300 μM [glibenclamide]. The response to step increases of internal [glibenclamide] could be resolved into two phases of channel inhibition (t1/2, fast, < 1 sec, t1/2, slow= 10.5 ± 0.9 sec, n = 8). Step decrease of [glibenclamide] caused a single resolvable phase of reactivation (t1/2= 20.4 ± 0.7 sec, n = 16). Channel inhibition by internal glibenclamide could be relieved by ADP, but only in the presence of Mg2+.