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Tyrosine kinase‐dependent modulation by interferon‐α of the ATP‐sensitive K+ current in rabbit ventricular myocytes

Tyrosine kinase‐dependent modulation by interferon‐α of the ATP‐sensitive K+ current in rabbit... We examined the effects of interferon‐α on the ATP‐sensitive K+ current (I K,ATP) in rabbit ventricular cells using the patch‐clamp technique. I K,ATP was induced by NaCN. Whole‐cell experiments indicated that interferon‐α (5×102–2.4×104 U/ml) inhibited I K,ATP in a concentration‐dependent manner (60.7±7.5% with 2.4×104 U/ml). In cell‐attached configuration, interferon‐α (2.4×104 U/ml) applied to the external solution also inhibited the activity of the single ATP‐sensitive K+ (KATP) channel by 56.0±5.8% without affecting the single channel conductance. The inhibitory effect of I K,ATP by interferon‐α was blocked by genistein and herbimycin A, tyrosine kinase inhibitors, but was not affected by N‐(2‐metylpiperazyl)‐5‐isoquinolinesulfoamide (H‐7), an inhibitor of protein kinase C and cAMP‐dependent protein kinase. These findings suggest that interferon‐α inhibits the cardiac KATP channel through the activation of tyrosine kinase. The tyrosine kinase‐mediated inhibition of I K,ATP by cytokines may aggravate cell damage during myocardial ischemia. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Febs Letters Wiley

Tyrosine kinase‐dependent modulation by interferon‐α of the ATP‐sensitive K+ current in rabbit ventricular myocytes

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References (31)

Publisher
Wiley
Copyright
© 2015 Federation of European Biochemical Societies
eISSN
1873-3468
DOI
10.1016/S0014-5793(99)00083-6
Publisher site
See Article on Publisher Site

Abstract

We examined the effects of interferon‐α on the ATP‐sensitive K+ current (I K,ATP) in rabbit ventricular cells using the patch‐clamp technique. I K,ATP was induced by NaCN. Whole‐cell experiments indicated that interferon‐α (5×102–2.4×104 U/ml) inhibited I K,ATP in a concentration‐dependent manner (60.7±7.5% with 2.4×104 U/ml). In cell‐attached configuration, interferon‐α (2.4×104 U/ml) applied to the external solution also inhibited the activity of the single ATP‐sensitive K+ (KATP) channel by 56.0±5.8% without affecting the single channel conductance. The inhibitory effect of I K,ATP by interferon‐α was blocked by genistein and herbimycin A, tyrosine kinase inhibitors, but was not affected by N‐(2‐metylpiperazyl)‐5‐isoquinolinesulfoamide (H‐7), an inhibitor of protein kinase C and cAMP‐dependent protein kinase. These findings suggest that interferon‐α inhibits the cardiac KATP channel through the activation of tyrosine kinase. The tyrosine kinase‐mediated inhibition of I K,ATP by cytokines may aggravate cell damage during myocardial ischemia.

Journal

Febs Letters – Wiley

Published: Feb 19, 1999

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