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.