| 12740420 |
Yamanaka J, Nishimura J, Hirano K, Kanaide H: An important role for the Na+-Ca2+ exchanger in the decrease in cytosolic Ca2+ concentration induced by isoprenaline in the porcine coronary artery. J Physiol. 2003 Jun 1;549(Pt 2):553-62. Epub 2003 May 9.
The role of the Na+-Ca2+ exchanger (NCX) in the mechanism of the isoprenaline (Iso)-induced vasorelaxation was investigated by simultaneously monitoring the intracellular Ca2+ concentration ([Ca2+] i) and tension of fura-2-loaded medial strips of porcine coronary arteries. Normal physiological salt solution (PSS) contained 137.3 mM Na+ and 5.9 mM K+. During the sustained phase of contraction, Iso induced only a transient decrease in [Ca2+] i when contraction was induced by depolarization with 118 mM K+ solution containing 25.2 mM Na+. When contraction was induced with 30 mM K+ in PSS containing 113.2 mM Na+, Iso induced a sustained decrease in [Ca2+] i, whereas in contractions induced by 30 mM K+ in a low Na+ (25.2 mM Na+) PSS, Iso transiently decreased [Ca2+] i. Replacement of Ca2+ with Ba2+ (which cannot be extruded by the Ca2+ pumps but can be extruded through the NCX) resulted in decreased [Ba2+] i induced by Iso in normal but not in low Na+ PSS. On the other hand, Iso induced a sustained decrease in [Ca2+] i when strips were pre-contracted by U46619, a thromboxane A2 analogue, in PSS. Various types of K+ channel blockers (iberiotoxin, 4-aminopyridine, apamin or glibenclamide) or combinations of these blockers failed to completely inhibit the Iso-induced decreases in [Ca2+] i and tension. However, Iso-induced sustained decreases in [Ca2+] i during the contraction induced by U46619 were greatly inhibited in a low Na+ PSS. The Iso-induced decrease in tension during contraction by U46619 was greatly inhibited by 2',4'-dichlorobenzamil, a forward- and reverse-mode NCX inhibitor, but not by ouabain, a selective inhibitor of Na+,K+-ATPase. These results indicate that the NCX is involved in the Iso-induced reduction of [Ca2+] i and tension of the porcine coronary arterial smooth muscle. |
0(0,0,0,0) |