Na<SUP>⁢</SUP>-Ca<SUP>2⁢</SUP> Exchange Curtails Ca<SUP>2⁢</SUP> before Its Diffusion to Global Ca<SUP>2⁢</SUP><SUB>i</SUB> in the Rat Ventricular Myocyte
Na<SUP>⁢</SUP>-Ca<SUP>2⁢</SUP> Exchange Curtails Ca<SUP>2⁢</SUP> before Its Diffusion to Global Ca<SUP>2⁢</SUP><SUB>i</SUB> in the Rat Ventricular Myocyte
- Sung-Wan Ahn Chang Mann Ko
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제9권 제2호
- 등재여부 : KCI등재
- 2005.01
- 95 - 102 (8 pages)
In the heart, Na<SUP>⁢</SUP>-Ca<SUP>2⁢</SUP> exchange (NCX) is the major Ca<SUP>2⁢</SUP> extrusion mechanism. NCX has been considered as a relaxation mechanism, as it reduces global [Ca<SUP>2⁢</SUP>]<SUB>i</SUB> raised during activation. However, if NCX locates in the close proximity to the ryanodine receptor, then NCX would curtail Ca<SUP>2⁢</SUP> before its diffusion to global Ca<SUP>2⁢</SUP><SUB>i</SUB>. This will result in a global [Ca<SUP>2⁢</SUP>]<SUB>i</SUB> 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 Ca<SUP>2⁢</SUP> after its release from SR in the presence and absence of global Ca<SUP>2⁢</SUP><SUB>i</SUB> transient in the isolated single rat ventricular myocytes by using patch-clamp technique in a whole-cell configuration. Global Ca<SUP>2⁢</SUP><SUB>i</SUB> transient was controlled by an internal dialysis with different con</SUB>centrations of BAPTA added in the pipette. During stimulation with a ramp pulse from ⁢100 mV to ⁣100 mV for 200 ms, global Ca<SUP>2⁢</SUP><SUB>i</SUB> 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 100μmol/L ryanodine, Na<SUP>⁢</SUP> depletion, 5 mmol/L NiCl<SUB>2</SUB> and 1μmol/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 Ca<SUP>2⁢</SUP> extrusion occurs before the Ca<SUP>2⁢</SUP> diffuses to global Ca<SUP>2⁢</SUP><SUB>i</SUB> in the rat ventricular myocyte.