Modulation of the sarcolemmal L-type current by alteration in SR Ca2+ release.
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 (V0.5) of the L-type current from 1.1 +/- 2.1 to -7.7 +/- 1.7 mV. Ruthenium red in the internal solution shifted V0.5 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 V0.5 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.
Balog
E M
EM
Department of Veterinary PathoBiology, University of Minnesota, St. Paul, Minnesota 55108, USA.
Gallant
E M
EM
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D018408:Patch-Clamp Techniques; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000502:physiology; D012508:Sarcolemma / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D002614:Chelating Agents; D019837:Ryanodine Receptor Calcium Release Channel; D012430:Ruthenium Red; D012433:Ryanodine; D002110:Caffeine; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium