scholarly journals Modulation of the sarcolemmal L-type current by alteration in SR Ca2+ release

1999 ◽  
Vol 276 (1) ◽  
pp. C128-C135 ◽  
Author(s):  
Edward M. Balog ◽  
Esther M. Gallant
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Ruthenium Red ◽  
Tetraacetic Acid ◽  
Internal Perfusion ◽  
Extracellular Solution ◽  
Internal Solution ◽  
Excitation Contraction Coupling ◽  
Peak Current ◽  
Contraction Coupling ◽  
Acid Perfusion

Modulation of the L-type current by sarcoplasmic reticulum (SR) Ca2+ release has been examined in patch-clamped mouse myotubes. Inhibition of SR Ca2+ release by inclusion of ryanodine in the internal solution shifted the half-activating voltage ( V 0.5) of the L-type current from 1.1 ± 2.1 to −7.7 ± 1.7 mV. Ruthenium red in the internal solution shifted V 0.5 from 5.4 ± 1.9 to −3.2 ± 4.1 mV. Chelation of myoplasmic Ca2+ with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid perfusion shifted V 0.5 from 4.4 ± 1.7 to −3.5 ± 3.3 mV and increased the peak current. Extracellular caffeine (1 mM), which should enhance SR Ca2+ release, significantly decreased the peak Ca2+ current. In low (0.1 mM) internal EGTA, myotube contraction was abolished by internal perfusion with ryanodine or ruthenium red, whereas addition of caffeine to the extracellular solution lowered the contractile threshold, indicating that these modulators of SR Ca2+ release had the expected effects on contraction. Therefore, SR Ca2+ release appears to modulate the sarcolemmal L-type current, suggesting a retrograde communication from the SR to the sarcolemmal L-type channels in excitation-contraction coupling.

Ryanodine modifies conductance and gating behavior of single Ca2+ release channel

1987 ◽  
Vol 253 (3) ◽  
pp. C364-C368 ◽  
Author(s):  
E. Rousseau ◽  
J. S. Smith ◽  
G. Meissner
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Lipid Bilayers ◽  
Single Channel ◽  
Ruthenium Red ◽  
Planar Lipid Bilayers ◽  
Open Probability ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling

Ryanodine affects excitation-contraction coupling in skeletal and cardiac muscle by specifically interacting with the sarcoplasmic reticulum (SR) Ca2+ release channel. The effect of the drug at the single channel level was studied by incorporating skeletal and cardiac SR vesicles into planar lipid bilayers. The two channels were activated by micromolar free Ca2+ and millimolar ATP and inhibited by Mg2+ and ruthenium red. Addition of micromolar concentrations of ryanodine decreased about twofold the unit conductance of the Ca2+- and ATP-activated skeletal and cardiac channels. A second effect of ryanodine was to increase the open probability (Po) of the channels in such a way that Po was close to unity under a variety of activating and inactivating conditions. The effects of ryanodine were long lasting in that removal of ryanodine by perfusion did not return the channels into their fully conducting state.

Calmodulin and Excitation-Contraction Coupling

Physiology ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 281-284 ◽  
Author(s):  
Susan L. Hamilton ◽  
Irina Serysheva ◽  
Gale M. Strasburg
Keyword(s):  
Skeletal Muscle ◽  
Ion Channels ◽  
Sarcoplasmic Reticulum ◽  
Release Channel ◽  
Excitation Contraction Coupling ◽  
Transverse Tubule ◽  
Contraction Coupling ◽  
Voltage Dependent ◽  
Important Regulator ◽  
Precise Role

Excitation-contraction coupling in cardiac and skeletal muscle involves the transverse-tubule voltage-dependent Ca2+ channel and the sarcoplasmic reticulum Ca2+ release channel. Both of these ion channels bind and are modulated by calmodulin in both its Ca2+-bound and Ca2+-free forms. Calmodulin is, therefore, potentially an important regulator of excitation-contraction coupling. Its precise role, however, has not yet been defined.

Potentiation of the halothane-cooling contractures of mammalian muscles by denervation

1990 ◽  
Vol 68 (9) ◽  
pp. 1207-1213 ◽  
Author(s):  
Margarete M. Trachez ◽  
R. Takashi Sudo ◽  
G. Suarez-Kurtz
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Soleus Muscle ◽  
Extensor Digitorum Longus ◽  
Extensor Digitorum ◽  
Tension Development ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Denervated Muscles

Denervation potentiated the cooling-induced contractures and the halothane-cooling contractures of isolated extensor digitorum longus and soleus muscles of the mouse. These effects were more striking in extensor digitorum longus than in soleus muscles. Significant increases in the peak amplitudes of the halothane-cooling contractures of both muscles and of the cooling contractures of soleus muscle were observed within 2 and 7 days of denervation. The potentiation of the contractures persisted for 90 days, the period of this study. Denervation (>2 days) endowed extensor digitorum longus with the ability to generate cooling contractures in the absence of halothane. The rate of tension development of cooling-induced contractures in the absence or presence of halothane was significantly greater in denervated (2–90 days) than in innervated muscles. Denervation also reduced the effectiveness of procaine in inhibiting the halothane-cooling contractures. It is proposed that the potentiation of cooling-induced contractures in denervated muscles results primarily from an increase in the rate of efflux and in the quantity of Ca2+ released from the sarcoplasmic reticulum, upon cooling and (or) when challenged with halothane.Key words: denervation, excitation–contraction coupling, halothane, cooling-induced contractures, skeletal muscle.

scholarly journals The recombinant dihydropyridine receptor II–III loop and partly structured ‘C’ region peptides modify cardiac ryanodine receptor activity

2005 ◽  
Vol 385 (3) ◽  
pp. 803-813 ◽  
Author(s):  
Angela F. DULHUNTY ◽  
Yamuna KARUNASEKARA ◽  
Suzanne M. CURTIS ◽  
Peta J. HARVEY ◽  
Philip G. BOARD ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Secondary Structure ◽  
Cardiac Muscle ◽  
Ryanodine Receptor ◽  
Structure Analysis ◽  
Room Temperature ◽  
Random Coil ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling

A physical association between the II–III loop of the DHPR (dihydropryidine receptor) and the RyR (ryanodine receptor) is essential for excitation–contraction coupling in skeletal, but not cardiac, muscle. However, peptides corresponding to a part of the II–III loop interact with the cardiac RyR2 suggesting the possibility of a physical coupling between the proteins. Whether the full II–III loop and its functionally important ‘C’ region (cardiac DHPR residues 855–891 or skeletal 724–760) interact with cardiac RyR2 is not known and is examined in the present study. Both the cardiac DHPR II–III loop (CDCL) and cardiac peptide (Cc) activated RyR2 channels at concentrations >10 nM. The skeletal DHPR II–III loop (SDCL) activated channels at ≤100 nM and weakly inhibited at ≥1 μM. In contrast, skeletal peptide (Cs) inhibited channels at all concentrations when added alone, or was ineffective if added in the presence of Cc. Ca2+-induced Ca2+ release from cardiac sarcoplasmic reticulum was enhanced by CDCL, SDCL and the C peptides. The results indicate that the interaction between the II–III loop and RyR2 depends critically on the ‘A’ region (skeletal DHPR residues 671–690 or cardiac 793–812) and also involves the C region. Structure analysis indicated that (i) both Cs and Cc are random coil at room temperature, but, at 5 °C, have partial helical regions in their N-terminal and central parts, and (ii) secondary-structure profiles for CDCL and SDCL are similar. The data provide novel evidence that the DHPR II–III loop and its C region interact with cardiac RyR2, and that the ability to interact is not isoform-specific.

Differential Effects of Fentanyl and Morphine on Intracellular Ca2+Transients and Contraction in Rat Ventricular Myocytes 

1998 ◽  
Vol 89 (6) ◽  
pp. 1532-1542 ◽  
Author(s):  
Noriaki Kanaya ◽  
Daniel R. Zakhary ◽  
Paul A. Murray ◽  
Derek S. Damron
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Myocardial Contractility ◽  
Ventricular Myocytes ◽  
Free Acid ◽  
Intact Cells ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Rat Ventricular Myocytes ◽  
Fura 2 ◽  
Cardiac Excitation

Background Our objective was to elucidate the direct effects of fentanyl and morphine on cardiac excitation-contraction coupling using individual, field-stimulated rat ventricular myocytes. Methods Freshly isolated myocytes were loaded with fura-2 and field stimulated (0.3 Hz) at 28 degrees C. Amplitude and timing of intracellular Ca2+ concentration (at a 340:380 ratio) and myocyte shortening (video edge detection) were monitored simultaneously in individual cells. Real time Ca2+ uptake into isolated sarcoplasmic reticulum vesicles was measured using fura-2 free acid in the extravesicular compartment. Results The authors studied 120 cells from 30 rat hearts. Fentanyl (30-1,000 nM) caused dose-dependent decreases in peak intracellular Ca2+ concentration and shortening, whereas morphine (3-100 microM) decreased shortening without a concomitant decrease in the Ca2+ transient. Fentanyl prolonged the time to peak and to 50% recovery for shortening and the Ca2+ transient, whereas morphine only prolonged the timing parameters for shortening. Morphine (100 microM), but not fentanyl (1 microM), decreased the amount of Ca2+ released from intracellular stores in response to caffeine in intact cells, and it inhibited the rate of Ca2+ uptake in isolated sarcoplasmic reticulum vesicles. Fentanyl and morphine both caused a downward shift in the dose-response curve to extracellular Ca2+ for shortening, with no concomitant effect on the Ca2+ transient. Conclusions Fentanyl and morphine directly depress cardiac excitation-contraction coupling at the cellular level. Fentanyl depresses myocardial contractility by decreasing the availability of intracellular Ca2+ and myofilament Ca2+ sensitivity. In contrast, morphine depresses myocardial contractility primarily by decreasing myofilament Ca2+ sensitivity.

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