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On the Mechanism of Inhibition of K ATP Channels by Glibenclamide in Rat Ventricular Myocytes
Author(s) -
RIPOLL CRISTINA,
LEDERER W.,
NICHOLS COLIN G.
Publication year - 1993
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1993.tb01210.x
Subject(s) - glibenclamide , biophysics , potassium channel , mechanism of action , medicine , membrane potential , pharmacology , conductance , endocrinology , biochemistry , chemistry , biology , in vitro , physics , diabetes mellitus , condensed matter physics
Glibenclamide Block of K ATP Channels. Introduction: The mechanism by which glibenclamide inhibits K ATP 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 K ATP 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 (t 1/2, fast , < 1 sec, t 1/2, slow = 10.5 ± 0.9 sec, n = 8). Step decrease of [glibenclamide] caused a single resolvable phase of reactivation (t 1/2 = 20.4 ± 0.7 sec, n = 16). Channel inhibition by internal glibenclamide could be relieved by ADP, but only in the presence of Mg 2+ . Conclusion: Glibenclamide can inhibit K ATP channels from either side of the membrane, with block from one side being competitive with block from the other. Internal MgADP antagonizes the blocking action of glibenclamide. Glibenclamide inhibition of cardiac K ATP channels differs quantitatively and qualitatively from the inhibition of pancreatic K ATP channels.