Primary cultured human coronary myocytes (HCMs) derived from ischemic human
hearts express an atypical voltage-gated tetrodotoxin (TTX)-sensitive sodi
um current (I-Na). The whole-cell patch-clamp technique was used to study t
he properties of I-Na in HCMs. The variations of intracellular calcium ([Ca
2+](i)) and sodium ([Na+](i)) were monitored in non-voltage-clamped cells l
oaded with Fura-2 or benzofuran isophthalate, respectively, using microspec
trofluorimetry. The activation and steady-state inactivation properties of
I-Na determined a "window" current between -50 and -10 mV suggestive of a s
teady-state Na+ influx at the cell resting membrane potential. Consistent w
ith this hypothesis, the resting [Na+](i) was decreased by TTX (1 mu mol/L)
. In contrast, it was increased by Na+ channel agonists that also promoted
a large rise in [Ca2+](i). Veratridine (10 mu mol/L), toxin V from Anemonia
sulcata (0.1 mu mol/L), and N-bromoacetamide (300 mu mol/L) increased [Ca2
+](i) by 7- to 15-fold. This increase was prevented by prior application of
TTX or lidocaine (10 mu mol/L) and by the use of Na+-free or Ca2+-free ext
ernal solutions. The Ca2+-channel antagonist nicardipine (5 mu mol/L) block
ed the effect of veratridine on [Ca2+](i) only partially. The residual comp
onent disappeared when external Na+ was replaced by Li+ known to block the
Na+/Ca2+ exchanger. The resting [Ca2+](i) was decreased by TTX in some cell
s. In conclusion, I-Na regulates [Ca2+](i) in primary cultured HCMs, This r
egulation, effective at baseline, involves a tonic control of Ca2+ influx v
ia depolarization-gated Ca2+ channels and, to a lesser extent, via a Na+/Ca
2+ exchanger working in the reverse mode.