The mechanism of KATP channel inhibition by ATP.

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Abstract
Whole-cell L-type Ca2+ channel current was recorded in GH3 clonal rat pituitary cells using Ba2+ as a charge carrier. In the presence of the dihydropyridine agonist Bay K 8644, deactivation was best described by two exponential components with time constants of approximately 2 and approximately 8 ms when recorded at -40 mV. The slow component activated at more negative potentials than the fast component: Half-maximal activation for the slow and fast components occurred at approximately -15 and approximately 1 mV, respectively. The fast component was more sensitive to enhancement by racemic Bay K 8644 than the slow component: ED50fast = approximately 21 nM, ED50slow = approximately 74 nM. Thyrotropin-releasing hormone (TRH; 1 microM) inhibited the slow component by approximately 46%, whereas the fast component was inhibited by approximately 22%. TRH inhibition of total L-current showed some voltage dependence, but each Bay K 8644-revealed component of L-current was inhibited in a voltage-independent manner. Therefore, the apparent voltage dependence of TRH action is derived from complexities in channel gating rather than from relief of inhibition at high voltages. In summary, Bay K 8644-enhanced L-currents in GH3 cells consist of two components with different sensitivities to voltage, racemic Bay K 8644, and the neuropeptide TRH.