Role of an atypical Na channel in arterial pathophysiology.

Primary cultured human coronary myocytes, derived from patients with endsta ge heart failure (NYHA, classes III and IV) caused by an ischemic disease a nd undergoing heart transplantation, express a voltage-gated tetrodotoxin-s ensitive sodium current (I-Na). This current has atypical electrophysiologi cal and pharmacological properties and regulates intracellular sodium ([Na](i)) and calcium ([Ca2+](i)). Our work is aimed at identifying its role an d regulation of expression during pathophysiology. We currently investigate whether I-Na is expressed in vascular smooth muscl es cells (VSMCs) isolated from either healthy or diseased (atheromatous) ar teries in human and, in parallel, in pig, rabbit and rat. Cells were enzyma tically isolated, primary cultured and macroscopic I-Na were recorded using the whole cell patch clamp technique. We found that I-Na is expressed in V SMCs grown from human aortic (90%; n=48) and pulmonary (44%; n=16) arteries and in the human aortic cell line HAVSMC (94%: n=27). I-Na was also detect ed in pig coronary (60%; n=25) and rabbit aortic (47%; n=15) VSMCs, but not in rat aortic myocytes (n=30). These different I-Na were activated at simi lar range of potentials (similar to-45 mV), had similar sensitivity to tetr odotoxin (IC50 around 5 nM) and similar density (2 to 4 pA/pF). Their expre ssion was related to cell dedifferentiation in vitro. However. I-Na was obs erved more frequently in human myocytes derived from diseased arteries (isc hemic cardiopathy) than in those derived from healthy tissues (dilated card iopathy). In conclusion, I-Na may contribute to increase the basal arterial contracti lity and play a role in pathological situations including hypertension.