Effects of altered availability of Na+ on guinea-pig airway smooth muscle contractility.
The effects of altering the availability of sodium ions (Na+) on contractility of the guinea-pig isolated trachealis was examined using regimens which are reported to inhibit Na+/K+ ATPase activity (ouabain), Na+/H+ exchange (amiloride, ammonium ion (NH4+)) or Na+/Ca2+ exchange (reduced extracellular Na+). Inhibition of Na+/K+ ATPase and reversal of Na+/Ca2+ exchange resulted in increased 45Ca uptake and contraction of the trachealis by voltage-sensitive and voltage-insensitive mechanisms respectively. When Na+/H+ exchange was inhibited by amiloride the tissues relaxed to below their baseline tension. The relaxation was not due to reduced Ca2+ influx. Treatment with NH4+ produced a contractile response. Reduced extracellular Na+ caused a transient contraction as a result of reversal of the normal Na+/Ca2+ exchange process leading to accumulation of Ca2+ within the cell. Since the effects of amiloride and reduced extracellular sodium were different, it is unlikely that amiloride is acting primarily by inhibiting Na+/Ca2+ exchange. Amiloride reduced tissue sensitivity to methacholine and KCl without affecting Ca2+ influx. This may involve a secondary stimulation of Na+/Ca2+ exchange following changes in [Na+]i. Ouabain also reduced tissue sensitivity to methacholine and KCl. These findings suggest that Na+ are important in determining smooth muscle contractility. If NH4+ is altering pH then, at the concentrations used, the changes in [H+] were not sufficient to alter responses to the spasmogens.
Raeburn
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Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Centre, New Orleans.
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001682:Biological Availability; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D002132:Calcium Radioisotopes; D000644:Quaternary Ammonium Compounds; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D002118:Calcium