THE EFFECTS OF PHARMACOLOGICAL MODULATION OF K-ATP ON THE GUINEA-PIG ISOLATED DIAPHRAGM

The purpose of the present study was to investigate the functional con sequences of K-ATP modulation in the normal and the metabolically inhi bited guinea-pig isolated diaphragm using the K+ channel openers croma kalim, pinacidil, RP49356 idil)-tetrahydrothiopyran-2-carbothiamide-1- oxide) and ZM260384 -dihydro-2H-1,4-benzoxazine-4-yl)pyridine-N-oxide) and the K+ channel inhibitors glibenclamide, phentolamine and ciclazi ndol. All K+ channel openers accelerated the decline in function induc ed by intermittent tetanic contractions following metabolic inhibition and delayed the development of contracture. Cromakalim also improved the recovery of twitch tension following 10 min intermittent tetanic s timulation in the hypoxic guinea-pig diaphragm preparation. Of the Kchannel inhibitors rested, only ciclazindol, at the highest concentrat ion tested (10 mu M), significantly delayed the decline in tetanic ten sion following metabolic inhibition in the guinea-pig isolated diaphra gm. None of the inhibitors significantly accelerated the development o f contracture. All inhibitors however, antagonised the actions of the K+ channel opener, cromakalim. The results indicate that opening of K- ATP can accelerate the decline in function following metabolic inhibit ion in the guinea-pig isolated diaphragm. In the absence of K+ channel openers however, K-ATP does not appear to contribute to this decline under the conditions of the present study.