Affiliation:
1. the Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, London, UK.
Abstract
The relative contributions of L-type Ca
2+
current (I
Ca
) and Na
+
/Ca
2+
exchange to Ca
2+
influx during the cardiac action potential (AP) are unknown. In this study, we have used an AP recorded under physiological conditions as the command voltage applied to voltage-clamped ventricular myocytes. I
Ca
(measured as nifedipine-sensitive membrane current) had a complex multiphasic time course during the AP. Peak I
Ca
was typically 4 pA/pF, after which it rapidly declined (to about 60% of peak) during the rising phase of the cell-wide Ca
2+
transient before increasing to a second, more sustained component. The initial decline in I
Ca
was sensitive to the amount of Ca
2+
released by the sarcoplasmic reticulum (SR), and conditions that reduce the amplitude of the Ca
2+
transient (such as rest or brief application of caffeine) increased net Ca
2+
influx via I
Ca
. Dissection of the Na
+
/Ca
2+
exchange current at the start of the AP suggested that Ca
2+
influx via Na
+
/Ca
2+
exchange is less than 30% of that due to I
Ca
. From these data, we suggest that I
Ca
is the primary source of Ca
2+
that triggers SR Ca
2+
release, even at the highly depolarized membrane potentials associated with the AP. However, Ca
2+
influx via Na
+
/Ca
2+
exchange is not negligible and may activate some Ca
2+
release from the SR, especially when I
Ca
is reduced. We propose that SR Ca
2+
release inhibits I
Ca
within the same beat, thereby providing a negative feedback mechanism that may serve to limit Ca
2+
influx as well as to regulate the amount of Ca
2+
stored within the SR.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
111 articles.
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