Affiliation:
1. From the Departments of Medical Physiology and Medicine, The University of Calgary, Alberta, Canada.
Abstract
Abstract
Although each of the fundamental processes involved in excitation-contraction coupling in mammalian heart has been identified, many quantitative details remain unclear. The initial goal of our experiments was to measure both the transmembrane Ca
2+
current, which triggers contraction, and the Ca
2+
extrusion due to Na
+
-Ca
2+
exchange in a single ventricular myocyte. An action potential waveform was used as the command for the voltage-clamp circuit, and the membrane potential, membrane current, [Ca
2+
]
i
, and contraction (unloaded cell shortening) were monitored simultaneously. Ca
2+
-dependent membrane current during an action potential consists of two components: (1) Ca
2+
influx through L-type Ca
2+
channels (I
Ca-L
) during the plateau of the action potential and (2) a slow inward tail current that develops during repolarization negative to ≈−25 mV and continues during diastole. This slow inward tail current can be abolished completely by replacement of extracellular Na
+
with Li
+
, suggesting that it is due to electrogenic Na
+
-Ca
2+
exchange. In agreement with this, the net charge movement corresponding to the inward component of the Ca
2+
-dependent current (I
Ca-L
) was approximately twice that during the slow inward tail current, a finding that is predicted by a scheme in which the Ca
2+
that enters during I
Ca
is extruded during diastole by a 3 Na
+
–1 Ca
2+
electrogenic exchanger. Action potential duration is known to be a significant inotropic variable, but the quantitative relation between changes in Ca
2+
current, action potential duration, and developed tension has not been described in a single myocyte. We used the action potential voltage-clamp technique on ventricular myocytes loaded with indo 1 or rhod 2, both Ca
2+
indicators, to study the relation between action potential duration, I
Ca-L
, and cell shortening (inotropic effect). A rapid change from a “short” to a “long” action potential command waveform resulted in an immediate decrease in peak I
Ca-L
and a marked slowing of its decline (inactivation). Prolongation of the action potential also resulted in slowly developing increases in the magnitude of Ca
2+
transients (145±2%) and unloaded cell shortening (4.0±0.4 to 7.6±0.4 μm). The time-dependent nature of these effects suggests that a change in Ca
2+
content (loading) of the sarcoplasmic reticulum is responsible. Measurement of [Ca
2+
]
i
by use of rhod 2 showed that changes in the rate of rise of the [Ca
2+
]
i
transient (which in rat ventricle is due to the rate of Ca
2+
release from the sarcoplasmic reticulum) were closely correlated with changes in the magnitude and the time course of I
Ca-L
. These findings demonstrate that Ca
2+
release from the sarcoplasmic reticulum can be modulated by the action potential waveform as a result of changes in I
Ca-L
.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
192 articles.
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