RPTP mu and protein tyrosine phosphorylation regulate K+ channel mRNA expression in adult cardiac myocytes

Previously, we reported that cell-cell contact regulates K+ channel mRNA ex pression in cultured adult rat cardiac myocytes. Here we show that exposing cardiac myocytes to tyrosine kinase inhibitors (genistein, tyrphostin A25) , but not inactive analogs, prevents downregulation of Kv1.5 mRNA and upreg ulation of Kv4.2 mRNA normally observed when they are cultured under low-de nsity conditions. Furthermore, cardiac myocytes cocultured with cells that endogenously (Mv 1 Lu) or heterologously (Chinese hamster ovary cells) expr ess the receptor-type protein tyrosine phosphatase mu (RPTP mu) display Kv1 .5 mRNA levels paralleling that which was observed in myocytes cultured und er high-density conditions and in intact tissue. In contrast, myocytes cocu ltured with control cells failed to produce this response. Finally, it is s hown that Kv4.2 mRNA expression is unaffected by RPTP mu. These findings re veal that multiple tyrosine phosphorylation-dependent mechanisms control ca rdiac myocyte K+ channel genes. Furthermore, we conclude that RPTP mu speci fically regulates cardiac myocyte Kv1.5 mRNA expression. Thus this receptor protein tyrosine phosphatase may be important in responses to pathological conditions associated with the loss of cell-cell interactions in the heart .