%0 Journal Article %1 Beuc_1988_233 %A Beuckelmann, D. J. %A Wier, W. G. %D 1988 %J J. Physiol. %K , 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, 2475607 3-Pyridinecarboxylic Action Animals, Calcium, Carrier Cells, Concentration, Cultured, Electrophysiology, Exchanger, Gov't, Guinea In Intracellular Mathematics, Membrane Membranes, Methyl Myocardium, Nickel, Non-U.S. Osmolar P.H.S., Pigs, Potentials, Proteins, Research Reticulum, Ryanodine, Sarcolemma, Sarcoplasmic Sodium-Calcium Support, Tetrodotoxin, U.S. Verapamil, Vitro, acid, ester, %P 233--255 %T Mechanism of release of calcium from sarcoplasmic reticulum of guinea-pig cardiac cells. %V 405 %X 1. The mechanisms that control release of Ca$^2+$ from the sarcoplasmic reticulum (SR) of guinea-pig ventricular cells were studied by observing intracellular calcium concentration (Ca$^2+$i transients) and membrane currents in voltage-clamped guinea-pig ventricular myocytes perfused internally with Fura-2. 2. Sarcolemmal Ca$^2+$ current was identified through the use of tetrodotoxin (TTX) and Ca$^2+$ channel antagonists (verapamil) and agonists (Bay K 8644). 3. Changes in Ca$^2+$i attributable to release of Ca$^2+$ from the SR were identified through the use of ryanodine, which abolishes the ability of the SR to release Ca$^2+$. Ryanodine-sensitive increases in Ca$^2+$i could be elicited either by depolarization or by repolarization (from depolarizing pulses to relatively positive membrane potentials). 4. At appropriate voltages, it is the initial fast change in Ca$^2+$i elicited by either depolarization or repolarization that is abolished by ryanodine, and is defined here as ryanodine sensitive. 5. The amplitude of the ryanodine-sensitive Ca$^2+$i transient elicited by depolarization had a bell-shaped dependence on membrane potential with a maximum of about 500 nM at 10 mV, and with the upper minimum between 60 and 70 mV. Verapamil-sensitive current activated over approximately the same potential range as the Ca$^2+$i transient, with a peak amplitude at 10 mV, and a reversal potential of 65 mV. 6. When a holding potential of -68 mV and TTX (30 microM) were used, the most negative pulse potential at which activation of an inward current occurred was -49 mV while changes in Ca$^2+$i occurred at -43 mV. 7. Ryanodine-sensitive increases in Ca$^2+$i elicited by repolarization (tail transients) were maximal for repolarization to 0 mV. Smaller changes in Ca$^2+$i than maximal were elicited by repolarization to both more positive and more negative potentials than 0 mV. The peak amplitude of the verapamil-sensitive tail currents elicited by repolarization increased continuously as the membrane was repolarized to potentials more negative than 60 mV. 8. Increasing depolarizing pulse duration beyond 10-20 ms did not increase the amplitude of the Ca$^2+$i transient, but prolonged it. 9. The experimental results are compared to the predictions of two theories on the mechanism of excitation-contraction coupling: Ca$^2+$-induced release of Ca$^2+$ (CICR), as it has been formulated from data in skinned cardiac cells, and a charge-coupled release mechanism (CCRM), as it has been formulated to explain excitation-contraction coupling in skeletal muscle. 10. Some of the results are clearly not consistent with certain features of a charge-coupled release mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

@article{Beuc_1988_233, abstract = {1. The mechanisms that control release of {C}a$^{2+}$ from the sarcoplasmic reticulum (SR) of guinea-pig ventricular cells were studied by observing intracellular calcium concentration ([{C}a$^{2+}$]i transients) and membrane currents in voltage-clamped guinea-pig ventricular myocytes perfused internally with Fura-2. 2. Sarcolemmal {C}a$^{2+}$ current was identified through the use of tetrodotoxin ({TTX}) and {C}a$^{2+}$ channel antagonists (verapamil) and agonists (Bay K 8644). 3. Changes in [{C}a$^{2+}$]i attributable to release of {C}a$^{2+}$ from the SR were identified through the use of ryanodine, which abolishes the ability of the SR to release {C}a$^{2+}$. Ryanodine-sensitive increases in [{C}a$^{2+}$]i could be elicited either by depolarization or by repolarization (from depolarizing pulses to relatively positive membrane potentials). 4. At appropriate voltages, it is the initial fast change in [{C}a$^{2+}$]i elicited by either depolarization or repolarization that is abolished by ryanodine, and is defined here as ryanodine sensitive. 5. The amplitude of the ryanodine-sensitive [{C}a$^{2+}$]i transient elicited by depolarization had a bell-shaped dependence on membrane potential with a maximum of about 500 nM at 10 mV, and with the upper minimum between 60 and 70 mV. Verapamil-sensitive current activated over approximately the same potential range as the [{C}a$^{2+}$]i transient, with a peak amplitude at 10 mV, and a reversal potential of 65 mV. 6. When a holding potential of -68 mV and {TTX} (30 microM) were used, the most negative pulse potential at which activation of an inward current occurred was -49 mV while changes in [{C}a$^{2+}$]i occurred at -43 mV. 7. Ryanodine-sensitive increases in [{C}a$^{2+}$]i elicited by repolarization (tail transients) were maximal for repolarization to 0 mV. Smaller changes in [{C}a$^{2+}$]i than maximal were elicited by repolarization to both more positive and more negative potentials than 0 mV. The peak amplitude of the verapamil-sensitive tail currents elicited by repolarization increased continuously as the membrane was repolarized to potentials more negative than 60 mV. 8. Increasing depolarizing pulse duration beyond 10-20 ms did not increase the amplitude of the [{C}a$^{2+}$]i transient, but prolonged it. 9. The experimental results are compared to the predictions of two theories on the mechanism of excitation-contraction coupling: {C}a$^{2+}$-induced release of {C}a$^{2+}$ (CICR), as it has been formulated from data in skinned cardiac cells, and a charge-coupled release mechanism ({CCRM}), as it has been formulated to explain excitation-contraction coupling in skeletal muscle. 10. Some of the results are clearly not consistent with certain features of a charge-coupled release mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Beuckelmann, D. J. and Wier, W. G.}, biburl = {https://www.bibsonomy.org/bibtex/245a2b5b9e8d42ae50331728b939f89cf/hake}, description = {The whole bibliography file I use.}, interhash = {0289ff5c93c3f33a22e0fef19d653a27}, intrahash = {45a2b5b9e8d42ae50331728b939f89cf}, journal = {J. Physiol.}, key = 99, keywords = {, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, 2475607 3-Pyridinecarboxylic Action Animals, Calcium, Carrier Cells, Concentration, Cultured, Electrophysiology, Exchanger, Gov't, Guinea In Intracellular Mathematics, Membrane Membranes, Methyl Myocardium, Nickel, Non-U.S. Osmolar P.H.S., Pigs, Potentials, Proteins, Research Reticulum, Ryanodine, Sarcolemma, Sarcoplasmic Sodium-Calcium Support, Tetrodotoxin, U.S. Verapamil, Vitro, acid, ester,}, month = Nov, pages = {233--255}, pmid = {2475607}, timestamp = {2009-06-03T11:21:03.000+0200}, title = {Mechanism of release of calcium from sarcoplasmic reticulum of guinea-pig cardiac cells.}, volume = 405, year = 1988 }