Effects of dihydropyridine receptor II-III loop peptides on Ca(2+) release in skinned skeletal muscle fibers
| Autor: | D. George Stephenson, Roque El-Hayek, Noriaki Ikemoto, Graham D. Lamb |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Calcium Channels
L-Type Physiology Phosphodiesterase Inhibitors Molecular Sequence Data Muscle Fibers Skeletal chemistry.chemical_element Peptide Skeletal Muscle Fibers Calcium Buffers In Vitro Techniques Caffeine medicine Animals Magnesium Rats Long-Evans Amino Acid Sequence Muscle Skeletal chemistry.chemical_classification Dose-Response Relationship Drug Ryanodine receptor Chemistry Endoplasmic reticulum Depolarization Cell Biology Peptide Fragments Rats Sarcoplasmic Reticulum Biochemistry Biophysics Potassium Bufo marinus medicine.symptom Intracellular Muscle contraction Muscle Contraction |
| Zdroj: | American journal of physiology. Cell physiology. 279(4) |
| ISSN: | 0363-6143 |
| Popis: | In skeletal muscle fibers, the intracellular loop between domains II and III of the α1-subunit of the dihydropyridine receptor (DHPR) may directly activate the adjacent Ca2+release channel in the sarcoplasmic reticulum. We examined the effects of synthetic peptide segments of this loop on Ca2+release in mechanically skinned skeletal muscle fibers with functional excitation-contraction coupling. In rat fibers at physiological Mg2+concentration ([Mg2+]; 1 mM), a 20-residue skeletal muscle DHPR peptide [AS(20); Thr671-Leu690; 30 μM], shown previously to induce Ca2+release in a triad preparation, caused only small spontaneous force responses in ∼40% of fibers, although it potentiated responses to depolarization and caffeine in all fibers. The COOH-terminal half of AS(20)[AS(10)] induced much larger spontaneous responses but also caused substantial inhibition of Ca2+release to both depolarization and caffeine. Both peptides induced or potentiated Ca2+release even when the voltage sensors were inactivated, indicating direct action on the Ca2+release channels. The corresponding 20-residue cardiac DHPR peptide [AC(20); Thr793-Ala812] was ineffective, but its COOH-terminal half [AC(10)] had effects similar to AS(20). In the presence of lower [Mg2+] (0.2 mM), exposure to either AS(20)or AC(10)(30 μM) induced substantial Ca2+release. Peptide CS(100 μM), a loop segment reported to inhibit Ca2+release in triads, caused partial inhibition of depolarization-induced Ca2+release. In toad fibers, each of the A peptides had effects similar to or greater than those in rat fibers. These findings suggest that the A and C regions of the skeletal DHPR II-III loop may have important roles in vivo. |
| Databáze: | OpenAIRE |
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