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Tyrosine kinase‐dependent modulation by interferon‐α of the ATP‐sensitive K + current in rabbit ventricular myocytes
Author(s) -
Nishio Manabu,
Habuchi Yoshizumi,
Tanaka Hideo,
Morikawa Junichiro,
Okanoue Takeshi,
Kashima Kei
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00083-6
Subject(s) - tyrosine kinase , patch clamp , chemistry , protein kinase a , interferon , microbiology and biotechnology , kinase , biology , endocrinology , biophysics , biochemistry , signal transduction , receptor , immunology
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 (5×10 2 –2.4×10 4 U/ml) inhibited I K,ATP in a concentration‐dependent manner (60.7±7.5% with 2.4×10 4 U/ml). In cell‐attached configuration, interferon‐α (2.4×10 4 U/ml) applied to the external solution also inhibited the activity of the single ATP‐sensitive K + (K ATP ) 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 K ATP 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.