Affiliation:
1. From the Centre National de la Recherche Scientifique (G.B., C.C., J.F.Q., J.N., S.R.), Institut de Genetique Humaine; Service d’Anesthésie B et de Chirurgie Cardiovasculaire, Hôpital A. de Villeneuve (G.B., J.M.F.); and Centre National de la Recherche Scientifique UPR-9055 (G.D.), Montpellier, France.
Abstract
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 ([Ca
2+
]
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 μmol/L). In contrast, it was increased by Na
+
channel agonists that also promoted a large rise in [Ca
2+
]
i
. Veratridine (10 μmol/L), toxin V from
Anemonia sulcata
(0.1 μmol/L), and
N
-bromoacetamide (300 μmol/L) increased [Ca
2+
]
i
by 7- to 15-fold. This increase was prevented by prior application of TTX or lidocaine (10 μmol/L) and by the use of Na
+
-free or Ca
2+
-free external solutions. The Ca
2+
-channel antagonist nicardipine (5 μmol/L) blocked the effect of veratridine on [Ca
2+
]
i
only partially. The residual component disappeared when external Na
+
was replaced by Li
+
known to block the Na
+
/Ca
2+
exchanger. The resting [Ca
2+
]
i
was decreased by TTX in some cells. In conclusion,
I
Na
regulates [Ca
2+
]
i
in primary cultured HCMs. This regulation, effective at baseline, involves a tonic control of Ca
2+
influx via depolarization-gated Ca
2+
channels and, to a lesser extent, via a Na
+
/Ca
2+
exchanger working in the reverse mode.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Reference29 articles.
1. Glycerinated Skeletal and Smooth Muscle: Calcium and Magnesium Dependence
2. Signal transduction and regulation in smooth muscle
3. Ca2+-activated potassium channels and ATP-sensitive potassium channels as modulators of vascular tone
4. Hille B. Ionic Channels of Excitable Membranes . 2nd ed. Sunderland Mass: Sinauer Associates Inc; 1992.
5. Catterall WA. Molecular analysis of voltage-gated sodium channels in the heart and other tissues. In: Zipes DP Jalife J eds. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia Pa: W. B. Saunders Co Inc; 1995:1–11.
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