EFFECT OF METHYL ISOCYANATE ON RABBIT CARDIAC NA-ATPASE(, K+)

The present study describes the effect of methyl isocyanate (MIC) on r abbit cardiac microsomal Na+, K+-ATPase. Addition of MIC in vitro resu lted in dose-dependent inhibition of Na+, K+-ATPase, Mg2+-ATPase and K +-activated p-nitrophenyl phosphatase (K+-PNPPase). Activation of Na+, K+-ATPase by ATP in the presence of MIC showed a decrease in V-max wi th no change in K-m. Similarly, activation of K+ PNPPase by PNPP in th e presence of MIC showed a decrease in V-max with no change in K-m. Th e circular dichroism spectral studies revealed that MIC interaction wi th Na+, K+-ATPase led to a conformation of the protein wherein the sub strates Na+ and K+ were no longer able to bind at the Na+- and K+-acti vation sites. The data suggest that the inhibition of Na+, K+-ATPase w as non-competitive and occurred by interference with the dephosphoryla tion of the enzyme-phosphoryl complex.