Role of extracellular Ca2+ in diaphragmatic contraction: effects of ouabain, monensin, and ryanodine.
The effects of zero extracellular Ca2+ on the contractility of rat diaphragmatic strips in vitro were studied in conjunction with various pharmacological agents known to influence the intracellular Ca2+ concentration: the Na+ ionophore, monensin, and the Na(+)-K+ pump inhibitor, ouabain, which enhance [Ca2+]i, caffeine, which induces Ca2+ release from the sarcoplasmic reticulum (SR), and ryanodine, which prevents Ca2+ retention by the SR. The effect of increasing [Ca2+]i on diaphragmatic contraction was assessed by comparing contractions induced by 120 mM K+ in the small muscle strips before and after the addition of ouabain or monensin. Monensin (20 microM) and ouabain (1-100 microM) augmented contractions up to threefold. Treatment of diaphragm strips with 3 nM ryanodine increased baseline tension 360% above the original resting tension but only if the diaphragm was electrically stimulated concurrently; 100 microM ryanodine induced contracture in quiescent tissue. High K+ contractures were of greater magnitude in the presence of ryanodine compared with control, and relaxation time was prolonged by greater than 200%. Ca(2+)-free conditions ameliorated these actions of ryanodine. Ryanodine reduced contractions induced by 10 mM caffeine and nearly abolished them in Ca(2+)-free solution. The data demonstrate that extracellular Ca2+ is important in certain types of contractile responses of the diaphragm and suggest that the processes necessary to utilize extracellular Ca2+ are present in the diaphragm.
Zavecz
J H
JH
Department of Pharmacology, Louisiana State University Medical Center, Shreveport.
Anderson
W M
WM
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D003964:Diaphragm / Q000502:physiology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007474:Ion Exchange; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012132:Respiratory Muscles / Q000187:drug effects / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D012433:Ryanodine; D002110:Caffeine; D010042:Ouabain; D008985:Monensin; D012964:Sodium; D011188:Potassium; D002118:Calcium