Affiliation:
1. From the Third Department of Internal Medicine (H.S., K.Q., H.T.) and Photon Medical Research Center (H.H.), Hamamatsu University School of Medicine, Hamamatsu, Japan, Department of Physiology (K.S.G., D.M.B.), Loyola University Chicago, Maywood, Ill.
Abstract
Background
—The Na
+
/Ca
2+
exchange (NCX) extrudes Ca
2+
from cardiac myocytes, but it can also mediate Ca
2+
influx, load the sarcoplasmic reticulum with Ca
2+
, and trigger Ca
2+
release from the sarcoplasmic reticulum. In ischemia/reperfusion or digitalis toxicity, increased levels of intracellular [Na
+
] ([Na
+
]
i
) may raise levels of intracellular [Ca
2+
] ([Ca
2+
]
i
) via NCX, leading to cell injury and arrhythmia.
Methods and Results
—We used KB-R7943 (KBR) to selectively block Ca
2+
influx via NCX to study the role of NCX-mediated Ca
2+
influx in intact rat ventricular myocytes. Removing extracellular Na
+
caused [Ca
2+
]
i
to rise, due to Ca
2+
influx via NCX, and this was blocked by 90% with 5 μmol/L KBR. However, KBR did not alter [Ca
2+
]
i
decline due to NCX. Thus, we used 5 μmol/L KBR to selectively block Ca
2+
entry but not efflux via NCX. Under control conditions, 5 μmol/L KBR did not alter steady-state twitches, Ca
2+
transients, Ca
2+
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 [Ca
2+
]
i
and abolished the spontaneous Ca
2+
oscillations, but it did not prevent inotropy.
Conclusions
—In rat ventricular myocytes, Ca
2+
influx via NCX is not important for normal excitation-contraction coupling. Furthermore, the inhibition of Ca
2+
efflux alone (as [Na
+
]
i
rises) may be sufficient to cause glycoside inotropy. In contrast, Ca
2+
overload and spontaneous activity at high [Na
+
]
i
was blocked by KBR, suggesting that net Ca
2+
influx (not merely reduced efflux) via NCX is involved in potentially arrhythmogenic Ca
2+
overload.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
158 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献