ABSTRACT
The voltage-dependent Na channel is one of the principal protein molecules controlling excitability in a variety of excitable cells (including neurons and skeletal and cardiac muscle cells). In these cells, the voltage-dependent Na current, which is fast-activated and -inactivated, triggers action potentials. As a result of its electrophysiological properties, the membrane potential in these excitable cells can be kept at a low level (i.e., more negative) while still allowing voltage-dependent channel activation. It was long believed that fast Na channels did not exist in smooth muscle cells (SMCs), because action potentials were not blocked by tetrodotoxin (TTX), the puffer-fish toxin, but were inhibited by Ca channel blockers or by removal of extracellular Ca ions (1). However, application of the single-cell voltage-clamp method to dispersed cells, as in electrophysiological research carried out on SMCs in the early 1980s, revealed voltage-dependent Na channels to be present after all, and these channels have been commonly observed in neurons and cardiac muscle cells. The first to report the presence of a voltage-dependent Na current were Ame´de´e et al. (2) (in the pregnant rat myometrium on the basis of a binding assay) and Sturek and Hermsmeyer (3) (who directly demonstrated the presence of a fast Na current in rat cultured SMCs from the azygos vein). Soon afterward, we detected a highly
TTX-sensitive Na current in freshly dispersed pulmonary arterial SMCs from mature rabbits (4). Since then, the presence of fast Na channels has been reported in various SMCs, in addition to the above tissues [human colon (5), human aorta and coronary artery (6), human esophageal cells (7), rat portal vein (8), rat vena cava (9), rat colon (5), guinea pig ureter (10), pig aorta and coronary artery (6), rabbit aorta and coronary artery (6)]. Now, although the presence of fast Na channels in various SMCs is beyond doubt, the role played by these channels remains uncertain, largely because many SMCs have a high membrane potential (i.e., more positive), at which Na channels are readily inactivated.
