1. The purpose of this study was to determine whether mechanisms other
than Ca$^2+$ influx via L-type Ca$^2+$ current (ICa) might
contribute to activation of contraction in rat ventricular myocytes.
The whole-cell voltage-clamp technique was used with normal transmembrane
K$^+$ and Na$^+$ gradients at 34 degrees C. The sarcoplasmic
reticulum (SR) was conditioned with one to three prepulses to +100
mV for 100 ms. 2. Cell shortening (delta L) increased with test voltage
up to a plateau level at about +20 mV, beyond which cell shortening
remained fairly constant, thus describing a sigmoidal voltage dependence.
This relationship was obtained when holding potential (Vh) was either
-40 or -70 mV; however, greater shortening was obtained at the more
negative Vh. 3. The sigmoidal V-delta L relationship was converted
to a bell shape following the magnitude of ICa when internal Cs+
was substituted for K$^+$ and when the temperature was reduced
to 22 degrees C. 4. At 34 degrees C, block of ICa with nifedipine
(10 microM) decreased shortening by about 50\% but did not alter
the voltage dependence of delta L when Vh was either -40 or -70 mV.
Addition of Ni2+ (4-5 mM) blocked all remaining contractions. 5.
When cell shortening was triggered by an action potential voltage
clamp, there was again about 50\% of the contraction that was insensitive
to nifedipine but was blocked by Ni2+. 6. Our results demonstrate
that there is a significant contribution of a nifedipine-insensitive
mechanism to the activation of contraction. This mechanism is likely
to be reverse mode Na$^+$-Ca$^2+$ exchange since it appears
to be sensitive to both voltage and Ni2+. We conclude that a contribution
of reverse Na$^+$-Ca$^2+$ exchange to activation of excitation-contraction
coupling occurs in rat heart at near-physiological conditions which
include warm temperatures, normal transmembrane Na$^+$ and K$^+$
gradients and activation in response to an action potential.
%0 Journal Article
%1 Wass_1996_529
%A Wasserstrom, J. A.
%A Vites, A. M.
%D 1996
%J J. Physiol.
%K 8782114 Action Animals, Blockers, Calcium Calcium, Cats, Cesium, Channel Channels, Contraction, Electrophysiology, Factors, Function, Gov't, Heart Heart, Humans, In Infant, Myocardial Myocardium, Nifedipine, Non-U.S. P.H.S., Patch-Clamp Potassium, Potentials, Rats, Research Reticulum, Ryanodine, Sarcoplasmic Saxitoxin, Sodium Sodium, Sprague-Dawley, Support, Techniques, Temperature, Time U.S. Ventricles, Ventricular Vitro,
%P 529--542
%T The role of Na$^+$-Ca$^2+$ exchange in activation of excitation-contraction
coupling in rat ventricular myocytes.
%V 493 ( Pt 2)
%X 1. The purpose of this study was to determine whether mechanisms other
than Ca$^2+$ influx via L-type Ca$^2+$ current (ICa) might
contribute to activation of contraction in rat ventricular myocytes.
The whole-cell voltage-clamp technique was used with normal transmembrane
K$^+$ and Na$^+$ gradients at 34 degrees C. The sarcoplasmic
reticulum (SR) was conditioned with one to three prepulses to +100
mV for 100 ms. 2. Cell shortening (delta L) increased with test voltage
up to a plateau level at about +20 mV, beyond which cell shortening
remained fairly constant, thus describing a sigmoidal voltage dependence.
This relationship was obtained when holding potential (Vh) was either
-40 or -70 mV; however, greater shortening was obtained at the more
negative Vh. 3. The sigmoidal V-delta L relationship was converted
to a bell shape following the magnitude of ICa when internal Cs+
was substituted for K$^+$ and when the temperature was reduced
to 22 degrees C. 4. At 34 degrees C, block of ICa with nifedipine
(10 microM) decreased shortening by about 50\% but did not alter
the voltage dependence of delta L when Vh was either -40 or -70 mV.
Addition of Ni2+ (4-5 mM) blocked all remaining contractions. 5.
When cell shortening was triggered by an action potential voltage
clamp, there was again about 50\% of the contraction that was insensitive
to nifedipine but was blocked by Ni2+. 6. Our results demonstrate
that there is a significant contribution of a nifedipine-insensitive
mechanism to the activation of contraction. This mechanism is likely
to be reverse mode Na$^+$-Ca$^2+$ exchange since it appears
to be sensitive to both voltage and Ni2+. We conclude that a contribution
of reverse Na$^+$-Ca$^2+$ exchange to activation of excitation-contraction
coupling occurs in rat heart at near-physiological conditions which
include warm temperatures, normal transmembrane Na$^+$ and K$^+$
gradients and activation in response to an action potential.
@article{Wass_1996_529,
abstract = {1. The purpose of this study was to determine whether mechanisms other
than {C}a$^{2+}$ influx via L-type {C}a$^{2+}$ current (ICa) might
contribute to activation of contraction in rat ventricular myocytes.
The whole-cell voltage-clamp technique was used with normal transmembrane
{K}$^{+}$ and {N}a$^{+}$ gradients at 34 degrees C. The sarcoplasmic
reticulum (SR) was conditioned with one to three prepulses to +100
mV for 100 ms. 2. Cell shortening (delta L) increased with test voltage
up to a plateau level at about +20 mV, beyond which cell shortening
remained fairly constant, thus describing a sigmoidal voltage dependence.
This relationship was obtained when holding potential (Vh) was either
-40 or -70 mV; however, greater shortening was obtained at the more
negative Vh. 3. The sigmoidal V-delta L relationship was converted
to a bell shape following the magnitude of ICa when internal Cs+
was substituted for {K}$^{+}$ and when the temperature was reduced
to 22 degrees C. 4. At 34 degrees C, block of ICa with nifedipine
(10 microM) decreased shortening by about 50\% but did not alter
the voltage dependence of delta L when Vh was either -40 or -70 mV.
Addition of Ni2+ (4-5 mM) blocked all remaining contractions. 5.
When cell shortening was triggered by an action potential voltage
clamp, there was again about 50\% of the contraction that was insensitive
to nifedipine but was blocked by Ni2+. 6. Our results demonstrate
that there is a significant contribution of a nifedipine-insensitive
mechanism to the activation of contraction. This mechanism is likely
to be reverse mode {N}a$^{+}$-{C}a$^{2+}$ exchange since it appears
to be sensitive to both voltage and Ni2+. We conclude that a contribution
of reverse {N}a$^{+}$-{C}a$^{2+}$ exchange to activation of excitation-contraction
coupling occurs in rat heart at near-physiological conditions which
include warm temperatures, normal transmembrane {N}a$^{+}$ and {K}$^{+}$
gradients and activation in response to an action potential.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Wasserstrom, J. A. and Vites, A. M.},
biburl = {https://www.bibsonomy.org/bibtex/2a249478fa0545151f5705f18a5245b88/hake},
description = {The whole bibliography file I use.},
interhash = {22f5ab302dca5bc84e152bf59fa8ecaf},
intrahash = {a249478fa0545151f5705f18a5245b88},
journal = {J. Physiol.},
key = 25,
keywords = {8782114 Action Animals, Blockers, Calcium Calcium, Cats, Cesium, Channel Channels, Contraction, Electrophysiology, Factors, Function, Gov't, Heart Heart, Humans, In Infant, Myocardial Myocardium, Nifedipine, Non-U.S. P.H.S., Patch-Clamp Potassium, Potentials, Rats, Research Reticulum, Ryanodine, Sarcoplasmic Saxitoxin, Sodium Sodium, Sprague-Dawley, Support, Techniques, Temperature, Time U.S. Ventricles, Ventricular Vitro,},
month = Jun,
pages = {529--542},
pmid = {8782114},
timestamp = {2009-06-03T11:21:36.000+0200},
title = {The role of {N}a$^{+}$-{C}a$^{2+}$ exchange in activation of excitation-contraction
coupling in rat ventricular myocytes.},
volume = {493 ( Pt 2)},
year = 1996
}