Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled m1 muscarinic acetylcholine receptor

Inhibitory effects of genistein on ATP‐sensitive K+ channels in rabbit portal vein smooth muscle

“…Augmentation of such ionic currents by orthovanadate and their inhibition by genistein, but not by daidzein, is fully consistent with the e ects being produced via tyrosine phosphorylation. Interestingly, direct evidence has been obtained for phosphorylation of a delayed recti®er K + channel (Kv 1.2) by tyrosine kinase and its inhibition by a low concentration of genistein (8 mM) (Huang et al, 1993;Lev et al, 1995).…”

“…These include the NMDA (N-methyl-Daspartate) receptor-mediated Ca 2+ in¯ux in neurones (O'Dell et al, 1991;Wang & Salter, 1994), a cloned delayed recti®er potassium channel (Huang et al, 1993), a reconstituted nicotinic acetylcholine receptor current (Hop®eld et al, 1988), epithelial sodium transport in an A6 cultured cell-line (Matsumoto et al, 1993), non-selective cation channels in ileum smooth muscle cells (Inoue et al, 1994), calcium channels in vascular smooth muscle cells (Wijetunge et al, 1992;Wijetunge & Hughes, 1995) and swelling-activated chloride channels in atrial myocytes (Sorota, 1995). In the majority of these studies the function of the modulating e ect of tyrosine phosphorylation on ionic channels was examined by use of genistein, a speci®c inhibitor of protein tyrosine kinase.…”

“…These studies suggest tyrosine phosphorylation of tyrosine residues might be an important mechanism for channel regulation, in addition to the well-attested protein phosphorylation that occurs through serine/threonine kinases. It has also been found that various channels can be phosphorylated by tyrosine kinase and the e ect inhibited by tyrosine kinase inhibitors (Huang et al, 1993;Moss et al, 1995;Lev et al, 1995;Swope et al, 1995).…”

“…With regard to the ATP-sensitive K + current, the participation of a tyrosine kinase in the muscarinic inhibition of this current has been obtained in rabbit oesophageal smooth muscle cells and in RAK-K + channels co-expressed with muscarinic receptors in Xenopus oocytes (Huang et al, 1993;Hatakeyama et al, 1995). These authors showed that tyrosine kinase enhanced the muscarinic inhibition of the ATP-sensitive K + current through modulation of protein kinase C. However, there has been no report of a direct e ect of tyrosine kinase on ATP-sensitive K + channel activity.…”

“…Evidence has been accumulating for some years now that tyrosine kinases are involved in receptor-mediated current inhibition, and in contraction and cell-signalling (Williams, 1989;Tsuda. et al, 1991;Wijetunge et al, 1992;Huang et al, 1993;Hollenberg, 1994;Felder, 1995;Wang & Salter, 1994;Moss et al, 1995;Wijetunge & Hughes, 1995;Hatakeyama et al, 1996). These studies suggest tyrosine phosphorylation of tyrosine residues might be an important mechanism for channel regulation, in addition to the well-attested protein phosphorylation that occurs through serine/threonine kinases.…”