Effects of components of ischemia on the Kv4.3 current stably expressed in Chinese hamster ovary cells.
We investigated the effects of three components of ischemia: external acidosis (pH=6.0), extracellular hyperkalemia ([K(+)]=20 mmol/l), and resting membrane depolarization to -60 mV, on Kv4.3 current stably expressed in Chinese Hamster Ovary cells. We used single electrode whole cell patch clamp techniques to study changes in the current elicited. External acidosis caused a positive shift in the steady state activation curve from -13.4 +/- 2.1 mV to -3.3 +/- 1.5 mV (n=8, P=0.004) and the steady state inactivation curve from -56.5 +/- 0.4 mV to -46.7 +/- 0.5 mV (n=14, P<0.0001). Acidosis also caused an acceleration of recovery from inactivation with the t(1/2) decreasing from 306 ms (95% CI 287-327 ms) to 194 ms (95% CI 182-207 ms), (n=14, P<0.05). Hyperkalemia did not affect any of these parameters. Combined acidosis and hyperkalemia produced effects similar to those seen with acidosis. Changing the holding potential from -90 mV to -60 mV with test potentials of +5 and +85 mV decreased the peak currents by 34.1% and 32.4% respectively (n=14). However, in the presence of external acidosis the decrease in peak currents induced by changing the holding potential was less marked. In acidotic bath the peak current at -60 mV was reduced by only 13.6% at a test potential of +5 mV and 12.3% at a test potential of +85 mV (n=14). Taken together our data suggest that the membrane depolarization and changes in pH which occur under ischemic conditions would be accompanied by relative preservation of Kv4.3 currents and provide a molecular basis for the observation of preserved epicardial I(to) and epicardial action potential duration (APD) shortening in ischemia.
Singarayar
Suresh
S
Department of Medicine, The University of New South Wales and the Victor Chang Cardiac Research Institute, Sydney, Australia.
Singleton
Cameron
C
Tie
Hui
H
Wyse
Ken
K
Bursill
Jane
J
Bauskin
Asne
A
Wu
Wan
W
Valenzuela
Stella
S
Breit
Samuel
S
Campbell
Terence
T
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D018014:Gene Transfer Techniques; D006947:Hyperkalemia / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels; D014162:Transfection
D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels