Bimodal operation of the ryanodine-sensitive transducer calcium channel.
Ryanodine binds to the transducer calcium channel complex that links depolarization of the transverse tubule to calcium release from the terminal cisternae during excitation-contraction coupling of skeletal muscle. Ryanodine exerts a bimodal action on the transducer calcium channel complex depending upon membrane potential and concentration. When the transmembrane potential is at resting level (-90 mV inside cell vs outside), low concentrations of ryanodine 10(-10) M to 10(-8) M favor calcium influx from outside which in turn causes calcium release from the terminal cisternae via calcium operated calcium channels. The leak from the terminal cisternae is insufficient to cause contraction but does cause a large increase in aerobic energy utilization by the Ca-ATPase of the sarcoplasmic reticulum. When the transmembrane potential is made more positive (-40 mV) the transducer channel is opened to the terminal cisternae of sarcoplasmic reticulum and is maintained in an open state by ryanodine allowing calcium efflux from the terminal cisternae to the sarcoplasm. At higher concentrations of ryanodine the transducer-calcium channel becomes open to the terminal cisternae and its store of ionized calcium leaks from the terminal cisternae in sufficient quantities to cause a contracture. The ryanodine-sensitive calcium transducer calcium channel operates in a bimodal manner. At low concentrations less than 10(-4) M the ryanodine-sensitive transducer calcium channel is open to the lumen of the T-tubule and allows calcium to flow in and trigger further calcium release. At higher concentrations the ryanodine-sensitive transducer channel opens to allow a calcium efflux from the terminal cisternae in sufficient quantities to cause contracture.
Bianchi
C P
CP
Department of Pharmacology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Narayan
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011898:Ranidae; D012433:Ryanodine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
D015220:Calcium Channels; D012433:Ryanodine; D002118:Calcium