%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 }