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

• Published in: FEBS letters 1999-02, Vol.445 (1), p.87-91
• Main Authors: Nishio, Manabu, Habuchi, Yoshizumi, Tanaka, Hideo, Morikawa, Junichiro, Okanoue, Takeshi, Kashima, Kei
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; Adenosine Triphosphate - metabolism; Animals; Benzoquinones; EGTA, ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid; Enzyme Inhibitors - pharmacology; Genistein - pharmacology; H-7, N-(2-metylpiperazyl)-5-isoquinolinesulfoamide; Heart Ventricles - cytology; HEPES, N-2-hydroxyethyl-piperazine-N′-2-ethanesulfonic acid; I K,ATP, ATP-sensitive K+ current; Interferon-alpha - metabolism; Interferon-alpha - pharmacology; Interferon-α; KATP channel, ATP-sensitive K+ channel; Lactams, Macrocyclic; PKA, cAMP-dependent protein kinase; PKC, protein kinase C; Potassium channel; Potassium Channel Blockers; Potassium Channels - physiology; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Quinones - pharmacology; Rabbit; Rabbits; Rifabutin - analogs & derivatives; Tyrosine kinase; Ventricular myocyte
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)00083-6

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.