Modulation of Ca2+-activated K+ current by isoprenaline,carbachol, and phorbol ester in cultured (and fresh) rat aortic vascular smooth muscle cells |
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| Affiliation: | 1. Smooth Muscle Research Centre, Dundalk Institute of Technology, Dublin Road, Co. Louth, Ireland;2. Molecular Medicine Laboratories, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Co. Dublin, Ireland;1. Joint Department of Biomedical Engineering, University of North Carolina-Chapel Hill and North Carolina State University, Raleigh, NC, USA;2. Department of Bioengineering, Temple University, Philadelphia, PA, USA;1. University of Piraeus, GR-18534 Piraeus, Greece;2. École Polytechnique Fédérale de Lausanne (EPFL), LMAF, STI, CH-1015 Lausanne, Switzerland;1. Kazan State Medical University, Butlerov St., 49, 420012 Kazan, Russia;2. Kazan (Volga Region) Federal University, Kazan Kremlin St., 18, Russia;3. Subio Inc., Amami-shi, Japan;4. Japan Aerospace Exploration Agency, Tsukuba, Japan;5. Kazan Institute of Biochemistry and Biophysics of Russian Acad. Sci., box 30, 420111 Kazan, Russia;6. Institute of Biomedical Problems of Russian Acad. Sci., Нoroshovskoe shosse St., 76a, 123007 Moscow, Russia |
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| Abstract: | - 1.1. Effects of isoprenaline (ISO), carbachol, and phorbol ester on the outward K+ currents in single cultured (or fresh) rat aortic vascular smooth muscle (A7r5 and A-10) cells were examined using a whole-cell voltage-clamp (at room temperature 22°C).
- 2.2. With 10 mM EGTA in the pipette solution, the delayed rectifier K+ current (IK) was activated by Ca2+ at pCa 7 more than at pCa 10, and was TEA (10 mM) and apamin (200 nM) sensitive, which represents a Ca2+-activated K+ current (IKCa).
- 3.3. In cultured A7r5 cells, isoprenaline (1 and 5 μM) and carbachol (0.1 and 1 μM) inhibited IKCa. Phorbol ester, 4-β-phorbol-12, 13-dibutyrate (PDB), at 0.1 and 1 μM also inhibited IKCa and increased the inhibitory effects induced by isoprenaline (1 μM).
- 4.4. In fresh aortic cells, these drugs, at the same concentrations, also produced the similar effects.
- 5.5. In A-10 cells, PDB (1 μM) enhanced the transient outward current (4-AP-sensitive), but ISO (1 μM) inhibited the current.
- 6.6. These results suggest that the IKCa current would be inhibited by cyclic nucleotides (cAMP and cGMP) and also by PK-C stimulation, and thereby be directly contributed to excitation-contraction coupling of the vascular smooth muscle cells.
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