Intracellular protons inhibit transient outward K+ current in ventricular myocytes from diabetic rats

Zhi Xu, Kaushik P. Patel, George J. Rozanski

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

This study examined the effects of protons on cardiac ion channel function in early stages of diabetes mellitus. Transient outward (I(to)) and 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 concentration was controlled by independently varying the pH of buffered external or pipette (pH(p)) solutions. External acidification did not alter I(to) in diabetic rat myocytes when initiated after intracellular dialysis with standard ph(p) 7.2, but when these cells were dialyzed with acidic ph(p) (6.6 or 6.0), I(to) density was significantly reduced. Low ph(p) also reduced I(to) density more in cells from diabetic rats than in controls, whereas alkaline pH(p) had no effect on either group of cells compared with standard pH(p) 7.2. In control myocytes dialyzed with pH(p) 6.0, block of Na+/H+ exchange with 5-(N,N- dimethyl)-amiloride (DMA) or Na+-free external solution further reduced I(to) density compared with pH(p) 6.0 alone, whereas these treatments had less effect on acid-dialyzed cells from diabetic rats. Dialysis with pH(p) 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) density in both groups was significantly reduced by nearly the same amount. We conclude that intracellular protons inhibit I(to) channels in ventricular myocytes from diabetic and control rats, but that for a given acid load, inhibition is markedly greater in diabetics. This difference 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 these K+ channels exhibit dissimilar sensitivities to intracellular protons.

Original languageEnglish (US)
Pages (from-to)H2154-H2161
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume271
Issue number5 40-5
DOIs
StatePublished - Nov 1996

Keywords

  • acidosis
  • sodium/hydrogen exchange

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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