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Characterization of voltage-gated calcium currents in freshly isolated smooth muscle cells from rat tail main artery
G V Petkov1, F Fusi, S Saponara
1Department of Pharmacology, University of Vermont, College of Medicine, Burlington, VT, USA.
Abstract:
The aim of the present study was to characterize voltage-gated Ca2+ currents in smooth muscle cells freshly isolated from rat tail main artery in the presence of 5 mmol L(-1) external Ca2+. Calcium currents were identified on the basis of their voltage dependencies and sensitivity to nifedipine, Ni2+ and cinnarizine. In the majority of the cells studied, T- and L-type currents were observed, while the remaining cells showed predominantly L-type currents. In the latter group of cells, holding potential change from -50 to either -70 or -90 mV increased the corresponding inward current amplitude while its voltage activation threshold remained unchanged. The steady state inactivation of L-type Ca2+ channels showed half-maximal inactivation at -38 mV. A Ca2+-dependent inactivation was also evident. Nifedipine (3 micromol L(-1)) blocked L-type but not T-type Ca2+ currents. Ni2+ (50 micromol L(-1)) as well as cinnarizine (1 micromol L(-1)) suppressed the nifedipine-resistant, T-type component of the currents. At higher concentrations, both Ni2+ (0.3-1 mmol L(-1)) and cinnarizine (10 micromol L(-1)) blocked the net inward current. Replacement of Ca2+ with 10 mmol L(-)1 Ba2+ significantly increased the amplitude of L-type Ca2+ currents. These results demonstrate that smooth muscle cells freshly isolated from rat tail main artery may be divided into two populations, one expressing both L- and T-type and the other only L-type Ca2+ channels. Furthermore, this report shows that in arterial smooth muscle cells cinnarizine potently inhibited T-type currents at low concentrations (1 micromol L(-1)) but also blocked L-type Ca2+ currents at higher concentrations (10 micromol L(-1)).
Insights
This study identified two types of calcium channels (T-type and L-type) in rat tail artery smooth muscle cells. Different concentrations of cinnarizine affected these voltage-gated calcium channels differently.
Area of Science:
- Physiology
- Pharmacology
Background:
- Smooth muscle cells in blood vessels rely on voltage-gated calcium channels for contraction.
- Understanding the specific types and properties of these channels is crucial for cardiovascular research.
Purpose of the Study:
- To characterize the voltage-gated calcium currents in rat tail artery smooth muscle cells.
- To investigate the differential effects of nifedipine, Ni2+, and cinnarizine on T-type and L-type calcium currents.
Main Methods:
- Isolation of smooth muscle cells from rat tail main artery.
- Electrophysiological recordings to measure voltage-gated calcium currents.
- Pharmacological analysis using nifedipine, Ni2+, and cinnarizine.
Main Results:
- Two populations of cells were identified: one with both T- and L-type calcium currents, and another with predominantly L-type currents.
- Nifedipine selectively blocked L-type currents, while Ni2+ and cinnarizine (at low concentrations) inhibited T-type currents.
- Cinnarizine demonstrated concentration-dependent effects, blocking T-type currents at 1 µmol/L and L-type currents at 10 µmol/L.
Conclusions:
- Rat tail artery smooth muscle cells exhibit distinct populations based on their expression of T- and L-type calcium channels.
- Cinnarizine exhibits differential blockade of T-type and L-type calcium channels in arterial smooth muscle, with potential therapeutic implications.