INTRACELLULAR PROTONS INHIBIT TRANSIENT OUTWARD K+ CURRENT IN VENTRICULAR MYOCYTES FROM DIABETIC RATS

This study examined the effects of protons on cardiac ion channel func tion in early stages of diabetes mellitus. Transient outward (I-to) an d inward rectifier K+ (I-K1) currents were recorded by the whole cell, voltage-clamp technique in ventricular myocytes isolated from hearts of streptozotocin-induced diabetic and control rats. Proton concentrat ion was controlled by independently varying the pH of buffered externa l or pipette (pH(p)) solutions. External acidification did not alter I -to in diabetic rat myocytes when initiated after intracellular dialys is with standard pH(p) 7.2, but when these cells were dialyzed with ac idic pH(p) (6.6 or 6.0), I-to density was significantly reduced. Low p H(p) also reduced I-to density more in cells from diabetic rats than i n controls, whereas alkaline pH(p) had no effect on either group of ce lls compared with standard pH(p) 7.2. In control myocytes dialyzed wit h pH(p) 6.0, block of Na+/H+ exchange with 5-(N,N-dimethyl)-amiloride (DMA) or Na+/H+ external solution further reduced I-to density compare d with pH(p) 6.0 alone, whereas these treatments had less effect on ac id-dialyzed cells from diabetic rats. Dialysis with pH, to 6.0 did not alter I-K1 in either group of cells compared with standard pH(p) 7.2, but when done in the presence of DMA. or Na+-free conditions, I-K1 de nsity in both groups was significantly reduced by nearly the same amou nt, We conclude that intracellular protons inhibit I-to channels in ve ntricular myocytes from diabetic and control rats, but that for a give n acid load, inhibition Is markedly greater in diabetics. This differe nce may be explained by a diabetes-induced decrease in Na+/H+ exchange that limits proton extrusion during intracellular acidosis. Moreover, acidosis may differentially suppress I-to and I-K1, suggesting that t hese K+ channels exhibit dissimilar sensitivities to intracellular pro tons.