Regulation of Ca2+ homeostasis by atypical Na+ currents in cultured human coronary myocytes

Circ Res. 1999 Oct 1;85(7):606-13. doi: 10.1161/01.res.85.7.606.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arteries
  • Calcium / metabolism*
  • Cells, Cultured
  • Coronary Vessels / cytology
  • Coronary Vessels / metabolism*
  • Electric Conductivity
  • Homeostasis
  • Humans
  • Intracellular Membranes / metabolism
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism*
  • Osmolar Concentration
  • Sodium / metabolism
  • Sodium / physiology*
  • Sodium Channel Agonists
  • Sodium Channels / physiology

Substances

  • Sodium Channel Agonists
  • Sodium Channels
  • Sodium
  • Calcium