Characterization of a voltage-dependent Na+ current in human esophageal smooth muscle

Smooth muscle contraction is critical to peristalsis in the human esophagus, yet the nature of the channels mediating excitation remains to be elucidated. The objective of this study was to characterize the inward currents in human esophageal smooth muscle cells (HESMCs). Esophageal tissue was isolated from patients undergoing surgery for cancer and grown in primary culture, and currents were recorded using patch-clamp electrophysiology. Depolarization elicited inward current activating positive to -40 mV and peaking at 0 mV and consisting of transient and sustained components. The transient current was half activated at -16 mV and half inactivated at -67 mV. The transient current was abolished by removal of bath Na+ or application of TTX (IC50 similar to20 nM), whereas it persisted in the absence of bath Ca2+ or the presence of Cd2+. These data provide evidence that cultured HESMCs express voltage-dependent Na+ channels. RT-PCR revealed mRNA transcripts for Na-x, the "atypical" Na+ channel isoform, as well as Na(v)1.4. These studies provide the first evidence of Nav1.4 in smooth muscle and contribute to a model of excitation in HESMCs.