Un courant sodique atypique lié à la patho-physiologie artérielle?

Primary cultured human coronary myocytes, derived from patients with end-stage heart failure (NYHA, classes III and IV) caused by an ischemic disease and undergoing heart transplantation, express a voltage-gated tetrodotoxin-sensitive sodium current (I Na ). This current has atypical electrophysiological and pharmacological properties and regulates intracellular sodium ([Na + ] i ) and calcium ([Ca 2+ ] i ). Our work is aimed at identifying its role and regulation of expression during pathophysiology. We currently investigate whether I Na is expressed in vascular smooth muscles cells (VSMCs) isolated from either healthy or diseased (atheromatous) arteries in human and, in parallel, in pig, rabbit and rat. Cells were enzymatically isolated, primary cultured and macroscopic I Na were recorded using the whole cell patch clamp technique. We found that I Na is expressed in VSMCs 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 detected 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 similar range of potentials (∼-45 mV), had similar sensitivity to tetrodotoxin (IC 50 around 5 nM) and similar density (2 to 4 pA/pF). Their expression was related to cell dedifferentiation in vitro. However, I Na was observed more frequently in human myocytes derived from diseased arteries (ischemic cardiopathy) than in those derived from healthy tissues (dilated cardiopathy). In conclusion, I Na may contribute to increase the basal arterial contractility and play a role in pathological situations including hypertension.