MEMBRANE-DELIMITED ACTIVATION OF MUSCARINIC-K CURRENT BY AN ALBUMIN-ASSOCIATED FACTOR IN GUINEA-PIG ATRIAL MYOCYTES

Atrial myocytes obtained by enzymatic perfusion of hearts from adult guinea-pigs and cultured for 0-14 days were studied using different configurations of the patch-clamp technique. Activation of muscarinic K current [I-K(ACh)] in whole-cell voltage-clamp mode by strongly diluted sera from various sources could be mimicked by corresponding concentrations of albumin, but not by delipidated (''fatty-acid-free'') samples of albumin. In cell-attached membrane patches activity of I-K(ACh) channels was significantly higher than basal I-K(ACh) channel activity, if the pipette contained serum, whereas application of serum-containing solution to the cell outside the patch did not affect channel activity. In isolated inside-out membrane patches, strong I-K(ACh) activation by internal guanosine triphosphate (GTP, 5 mu M) was observed if the pipette contained serum. If no activator was presented to the outer face of the membrane, only weak opening activity was observed during bath application of GTP. These results demonstrate that the serrum factor which causes activation of I-K(ACh) is associated with albumin. Furthermore activation of I-K(ACh) by that factor proceeds analogous to ACh or adenosine, i. e. via a membrane-delimited receptor, G-protein, channel interaction.