Cell-cell contact between adult rat cardiac myocytes regulates Kv1.5 and Kv4.2 K+ channel mRNA expression

Regulation of voltage-gated K+ channel genes represents an important mechan ism for modulating cardiac excitability. Here we demonstrate that expressio n of two K+ channel mRNAs is reciprocally controlled by cell-cell interacti ons between adult cardiac myocytes. It is shown that culturing acutely diss ociated rat ventricular myocytes for 3 h results in a dramatic downregulati on of Kv1.5 mRNA and a modest upregulation of Kv4.2 mRNA. These effects are specific, because similar changes are not detected with other channel mRNA s. Increasing myocyte density promotes maintenance of Kv1.5 gene expression , whereas Kv4.2 mRNA expression was found to be inversely proportional to c ell density. Conditioned culture medium did not mimic the effects of high c ell density. However, paraformaldehyde-fixed myocytes were comparable to li ve cells in their ability to influence K+ channel message levels. Thus the reciprocal effects of cell density on the expression of Kv1.5 and Kv4.2 gen es are mediated by direct contact between adult cardiac myocytes. These fin dings reveal for the first time that cardiac myocyte gene expression is inf luenced by signaling induced by cell-cell contact.