A NOVEL TETRODOTOXIN-SENSITIVE NA+ CURRENT IN CULTURED HUMAN CORONARYMYOCYTES

Voltage-gated Na+ currents (I(Na)s) are usually not found in arterial smooth muscle. We enzymatically isolated myocytes from the media of le ft coronary arteries of heart transplant patients with ischemic cardio pathy. Using the whole-cell voltage-clamp technique (20 degrees C to 2 2 degrees C), we detected no IN, in any of the freshly isolated myocyt es. 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 com prising a fast inactivating and sustained components that could not be separated by their electrophysiological and pharmacological propertie s. I-Na activated at depolarizations positive to -50 mV, was maximal a t 0 mV, and was available from relatively low resting membrane potenti als (half-inactivation at -46 mV). I-Na was modulated by several ligan ds known to bind selectively at different sites of Na+ channels. It wa s blocked with high affinity by tetrodotaxin (IC50, = 10 nmol/L) and l ocal anesthetics (bupivacaine and lidocaine; IC50, = 100 nmol/L) and b y Cd2+ (IC50, approximate to 300 mu mol/L). IN, was modulated by Na+ c hannel agonists such as toxin AsV from Anemonia sulcata and veratridin e, which slowed current kinetics dramatically. In conclusion, human co ronary myocytes in culture can express an atypical tetrodotoxin-sensit ive I-Na, with a large sustained component, which is expected to contr ibute to massive Na+ influx into these cells. Phenotypic modulation of the expression of this I-Na may be related to cell dedifferentiation and proliferation.