Ca2+ Channel Inactivation in Small Mesenteric Arteries of WKY and SHR

• Published in: American journal of hypertension 2008-04, Vol.21 (4), p.406-412
• Main Authors: Cox, Robert H., Lozinskaya, Irina M.
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Calcium Channels - metabolism; Cardiology. Vascular system; Disease Models, Animal; Hormones. Endocrine system; Hypertension - metabolism; Hypertension - pathology; Hypertension - physiopathology; Male; Medical sciences; Membrane Potentials - physiology; Mesenteric Arteries - metabolism; Mesenteric Arteries - pathology; Mesenteric Arteries - physiopathology; Muscle Cells - metabolism; Muscle Contraction - physiology; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Muscle, Smooth, Vascular - physiopathology; Patch-Clamp Techniques; Pharmacology. Drug treatments; Rats; Rats, Inbred SHR; Rats, Inbred WKY
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1038/ajh.2007.73

Background This study was designed to test the hypothesis that differences exist in the inactivation properties of voltage-gated Ca2+ channels (CaV) in hypertensive arterial smooth muscle cells (ASMCs), and that these differences contribute to enhanced CaV activity. Methods The properties of CaV were studied in freshly isolated myocytes from small mesenteric arteries (SMAs) of Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHRs) using whole-cell patch-clamp methods. Results Peak currents (ICa) were larger in SHR with either 2 mmol/l Ca2+ or Ba2+ as the charge carrier. In WKY and SHR, the peak current was larger with Ba2+ than with Ca2+ with no difference in their ratio. The voltage dependence of CaV activation was shifted to the left in SHR as compared to WKY for Ca2+ but not for Ba2+, while availability was not different. The time course of inactivation of current could be represented by two time constants, both of which were larger in SHR than in WKY and also larger for Ba2+ than for Ca2+, with a greater fraction of inactivation being associated with the process slower in SHR and with Ba2+. The time courses of availability, inactivation, and recovery from inactivation were faster in SHR than in WKY in the case of Ca2+, but there was no difference in the case of Ba2+. Conclusions These results demonstrate that there are differences between WKY and SHR in the inactivation properties of SMA CaV, and that these differences could contribute to larger steady-state currents. The differences cannot be explained merely by the presence of a larger number of identical CaV complexes, and it appears likely that differences in intrinsic compositions, primary structures, and/or regulation are involved.