Na(+)-K+ pump stimulation elicits recovery of contractility in K(+)-paralysed rat muscle.
1. This study explores the role of active electrogenic Na(+)-K+ transport in restoring contractility in isolated rat soleus muscles exposed to high extracellular potassium concentration ([K+]o). This was done using agents (catecholamines and insulin) known to stimulate the Na(+)-K+ pump via different mechanisms. 2. When exposed to Krebs-Ringer bicarbonate buffer containing 10 mM K+, the isometric twitch and tetanic force of intact muscles decreased by 40-69%. The major part of this decline could be prevented by the addition of salbutamol (10(-5) M). In the presence of 10 mM K+, force could be restored almost completely within 5-10 min by the addition of salbutamol or adrenaline and partly by insulin. 3. In muscles exposed to 12.5 mM K+, force declined by 96%. Salbutamol (10(-5) M), adrenaline (10(-6) M) and insulin (100 mU ml-1) produced 57-71, 61-71 and 38-47% recovery of force within 10-20 min, respectively. The effects of these supramaximal concentrations of salbutamol and insulin on force recovery were additive. Salbutamol and adrenaline produced significant recovery of contractility at concentrations down to 10(-8) M (P < 0.005). 4. In soleus, the same agents stimulated 86Rb+ uptake and decreased intracellular Na+. These actions reflect stimulation of active Na(+)-K+ transport and both showed a highly significant correlation to the recovery of twitch as well as tetanic force (r = 0.80-0.88; P < 0.001). 5. The force recovery induced by salbutamol, adrenaline and insulin was suppressed by pre-exposure to ouabain (10(-5) M for 10 min or 10(-3) M for 1 min) as well as by tetrodotoxin (10(-6) M). 6. The observations support the conclusion that the inhibitory effect of high [K+]o on contractility in skeletal muscle can be counterbalanced by stimulation of active electrogenic Na(+)-K+ transport, the ensuing increase in the clearance of extracellular K+ and in the transmembrane electrochemical gradient for Na+.
Clausen
T
T
Institute of Physiology, University of Aarhus, Denmark.
Andersen
S L
SL
Flatman
J A
JA
D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008985:Monensin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012413:Rubidium / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*
D007328:Insulin; D010042:Ouabain; D008985:Monensin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D000420:Albuterol; D011188:Potassium; D004837:Epinephrine