A Novel Tetrodotoxin-Sensitive Na sup + Current in Cultured Human Coronary Myocytes

Voltage-gated Na sup + currents (I Na s) are usually not found in arterial smooth muscle. We enzymatically isolated myocytes from the media of left coronary arteries of heart transplant patients with ischemic cardiopathy. Using the whole-cell voltage-clamp technique (20 degrees C to 22 degrees C), we detected no I Na in any of the freshly isolated myocytes. In contrast, when the cells were grown in culture, we could record a large I Na . This I Na was characterized by a biexponential decay comprising a fast inactivating and sustained components that could not be separated by their electrophysiological and pharmacological properties. I Na activated at depolarizations positive to -50 mV, was maximal at 0 mV, and was available from relatively low resting membrane potentials (half-inactivation at -46 mV). I Na was modulated by several ligands known to bind selectively at different sites of Na sup + channels. It was blocked with high affinity by tetrodotoxin (IC 50 , nearly =10 nmol/L) and local anesthetics (bupivacaine and lidocaine; IC 50 , nearly =100 nmol/L) and by Cd 2 + (IC 50 , nearly =300 micro mol/L). I Na was modulated by Na sup + channel agonists such as toxin AsV from Anemonia sulcata and veratridine, which slowed current kinetics dramatically. In conclusion, human coronary myocytes in culture can express an atypical tetrodotoxin-sensitive I Na with a large sustained component, which is expected to contribute to massive Na sup + influx into these cells. Phenotypic modulation of the expression of this I Na may be related to cell dedifferentiation and proliferation.