KB-R7943 block of Ca2+ influx via Na+/Ca2+ exchange does not alter twitches or glycoside inotropy but prevents Ca2+ overload in rat ventricular myocytes
H. Satoh et al., KB-R7943 block of Ca2+ influx via Na+/Ca2+ exchange does not alter twitches or glycoside inotropy but prevents Ca2+ overload in rat ventricular myocytes, CIRCULATION, 101(12), 2000, pp. 1441-1446
Citations number
39
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-The Na+/Ca2+ exchange (NCX) extrudes Ca2+ from cardiac myocytes,
hut it can also mediate Ca2+ influx, load the sarcoplasmic reticulum with
Ca2+, and trigger Ca2+ release from the sarcoplasmic reticulum. In ischemia
/reperfusion or digitalis toxicity, increased levels of intracellular [Na+]
([Na+](i)) may raise levels of intracellular [Ca2+] ([Ca2+](i)) via NCX, l
eading to cell injury and arrhythmia.
Methods and Results-We used KB-R7943 (KBR) to selectively block Ca2+ influx
via NCX to study the role of NCX-mediated Ca2+ influx in intact rat ventri
cular myocytes. Removing extracellular Na+ caused [Ca2+](i) to rise, due to
Ca2+ influx via NCX, and this was blocked by 90% with 5 mu mol/L KBR. Howe
ver, KBR did not alter [Ca2+](i) decline due to NCX. Thus, we used 5 mu mol
/L KBR to selectively block Ca2+ entry but not efflux via NCX. Under contro
l conditions, 5 mu mol/L KBR did not alter steady-state twitches, Ca2+ tran
sients, Ca2+ load in the sarcoplasmic reticulum, or rest potentiation, but
it did prolong the late low plateau of the rat action potential. When Na+/K
+ ATPase was inhibited by strophanthidin, KBR reduced diastolic [Ca2+](i) a
nd abolished the spontaneous Ca2+ oscillations, but it did not prevent inot
ropy.
Conclusions-In rat ventricular myocytes, Ca2+ influx via NCX is not importa
nt for normal excitation-contraction coupling. Furthermore, the inhibition
of Ca2+ efflux alone (as [Na+](i) rises) may be sufficient to cause glycosi
de inotropy. In contrast, Ca2+ overload and spontaneous activity at high [N
a+](i) was blocked by KBR, suggesting that net Ca2+ influx (not merely redu
ced efflux) via NCX is involved in potentially arrhythmogenic Ca2+ overload
.