Affiliation:
1. From The Johns Hopkins University, School of Medicine, Institute of Molecular Cardiobiology (A.A.A., I.A.H., G.F.T., B.O.’R.) and the Whitaker Biomedical Engineering Institute (A.A.A., R.L.W.), Baltimore, Md.
Abstract
Increased Na
+
-Ca
2+
exchange (NCX) activity in heart failure and hypertrophy may compensate for depressed sarcoplasmic reticular Ca
2+
uptake, provide inotropic support through reverse-mode Ca
2+
entry, and/or deplete intracellular Ca
2+
stores. NCX is electrogenic and depends on Na
+
and Ca
2+
transmembrane gradients, making it difficult to predict its effect on the action potential (AP). Here, we examine the effect of [Na
+
]
i
on the AP in myocytes from normal and pacing-induced failing canine hearts and estimate the direction of the NCX driving force using simultaneously recorded APs and Ca
2+
transients. AP duration shortened with increasing [Na
+
]
i
and was correlated with a shift in the reversal point of the NCX driving force. At [Na
+
]
i
≥10 mmol/L, outward NCX current during the plateau facilitated repolarization, whereas at 5 mmol/L [Na
+
]
i
, NCX had a depolarizing effect, confirmed by partially inhibiting NCX with exchange inhibitory peptide. Exchange inhibitory peptide shortened the AP duration at 5 mmol/L [Na
+
]
i
and prolonged it at [Na
+
]
i
≥10 mmol/L. With K
+
currents blocked, total membrane current was outward during the late plateau of an AP clamp at 10 mmol/L [Na
+
]
i
and became inward close to the predicted reversal point for the NCX driving force. The results were reproduced using a computer model. These results indicate that NCX plays an important role in shaping the AP of the canine myocyte, helping it to repolarize at high [Na
+
]
i
, especially in the failing heart, but contributing a depolarizing, potentially arrhythmogenic, influence at low [Na
+
]
i
.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
156 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