Na+-Ca2+ Exchange Curtails Ca2+ before Its Diffusion to Global Ca2+i in the Rat Ventricular Myocyte.
- Author:
Sung Wan AHN
1
;
Chang Mann KO
Author Information
1. Department of Pharmacology and Institute of Basic Medical Science, Yonsei University Wonju-College of Medicine, Wonju 220-701, Korea. changmko@wonju.yonsei.ac.kr
- Publication Type:Original Article
- Keywords:
Na+-Ca2+ exchange;
Global Ca2+i transient;
BAPTA;
Ryanodine receptor;
Ca2+-induced Ca2+ release
- MeSH:
Animals;
Architectural Accessibility;
Dialysis;
Diffusion*;
Heart;
Muscle Cells*;
Nifedipine;
Patch-Clamp Techniques;
Rats*;
Relaxation;
Ryanodine;
Ryanodine Receptor Calcium Release Channel
- From:The Korean Journal of Physiology and Pharmacology
2005;9(2):95-101
- CountryRepublic of Korea
- Language:English
-
Abstract:
In the heart, Na+-Ca2+ exchange (NCX) is the major Ca2+ extrusion mechanism. NCX has been considered as a relaxation mechanism, as it reduces global [Ca2+]i raised during activation. However, if NCX locates in the close proximity to the ryanodine receptor, then NCX would curtail Ca2+ before its diffusion to global Ca2+i. This will result in a global [Ca2+]i decrease especially during its ascending phase rather than descending phase. Therefore, NCX would decrease the myocardial contractility rather than inducing relaxation in the heart. This possibility was examined in this study by comparing NCX-induced extrusion of Ca2+ after its release from SR in the presence and absence of global Ca2+i transient in the isolated single rat ventricular myocytes by using patch-clamp technique in a whole-cell configuration. Global Ca2+i transient was controlled by an internal dialysis with different concentrations of BAPTA added in the pipette. During stimulation with a ramp pulse from +100 mV to -100 mV for 200 ms, global Ca2+i transient was suppressed only mildly, and completely at 1 mmol/L, and 10 mmol/L BAPTA, respectively. In these situations, ryanodine-sensitive inward NCX current was compared using 100micromol/L ryanodine, Na+ depletion, 5 mmol/L NiCl2 and 1micromol/L nifedipine. Surprisingly, the result showed that the ryanodine-sensitive inward NCX current was well preserved after 10 mmol/L BAPTA to 91 % of that obtained after 1 mmol/L BAPTA. From this result, it is concluded that most of the NCX-induced Ca2+ extrusion occurs before the Ca2+ diffuses to global Ca2+i in the rat ventricular myocyte.
