Influence of energy supply and calcium on the low sodium induced changes in the transmembrane potential and contraction of guinea pig papillary muscle

1970 ◽  
Vol 48 (4) ◽  
pp. 241-253 ◽  
Author(s):  
K. Prasad

The effects of changes in extracellular concentrations (25, 50, 100, 140 mM) of NaCl on the simultaneously recorded action potential (AP) and contraction of guinea pig papillary muscle in the presence of various concentrations of glucose (0, 5, 20, 30, 50 mM) and CaCl2 (0, 0.5, 1.0, 2.5 mM) were investigated. Low sodium (25 mM) produced a marked shortening of the action potential duration (APD) associated with a marked increase in the force of contraction but a small change in AP amplitude. A direct relation between extracellular NaCl and cardiac contraction was observed. There was no relation between AP amplitude and cardiac contraction. Low sodium induced shortening of the APD was greater in the absence of glucose than in its presence while the increase in the force contraction induced by low Na was markedly reduced in the absence of glucose. Low sodium was practically ineffective in restoring the contraction of papillary muscle in the absence of CaCl2. A calcium concentration dependent increase in the force of contraction was associated with a corresponding shortening of the APD in low sodium. Anoxia markedly reduced the positive inotropic effects of low sodium and enhanced the low sodium induced shortening of the APD in the papillary muscle. Glucose produced a marked lengthening of the APD which was shortened during anoxia but it was effective only slightly in lengthening the APD shortened by low sodium. The effects of ouabain in the muscles in the presence of low sodium were reduced. It is suggested that the changes in the APD accompanied by changes in the contraction in the guinea pig papillary muscle might be associated with NaCl-induced changes in the membrane ATPase. The low sodium induced increase in the force of contraction seems to be dependent upon both calcium and energy supply.

2010 ◽  
Vol 299 (3) ◽  
pp. R786-R792 ◽  
Author(s):  
Véronique Deschodt-Arsac ◽  
Guillaume Calmettes ◽  
Gérard Raffard ◽  
Philippe Massot ◽  
Jean-Michel Franconi ◽  
...  

Levosimendan is a calcium sensitizer developed for the treatment of heart failure. It increases contractile force by enhancing the sensitivity of myofilaments to calcium. Besides this sensitizing effect, the drug has also been reported to show some inhibitory action on phosphodiesterase 3 (PDE3). The inotropic effects of levosimendan have been studied on guinea pig paced perfused hearts by using modular control analysis (MoCA) (Diolez P, Deschodt-Arsac V, Raffard G, Simon C, Santos PD, Thiaudiere E, Arsac L, Franconi JM. Am J Physiol Regul Integr Comp Physiol 293: R13–R19, 2007.), an integrative approach of heart energetics using noninvasive 31P NMR. The aim was to evaluate quantitatively the respective effects of this drug on energy supply and demand modules. Under our experimental conditions, 0.7 μM levosimendan induced a 45% increase in paced heart output associated with a 7% decrease in phosphocreatine and a negligible increase in oxygen consumption. Because MoCA allows in situ study of the internal regulations in intact beating heart energetics, it was applied to describe quantitatively by which routes levosimendan exerts its inotropic action. MoCA demonstrated the absence of any significant effect of the drug on the supply module, which is responsible for the lower increase in oxygen consumption, compared with epinephrine, which increases the ratio between myocardial oxygen consumption and cardiac contraction. This result evidences that, under our conditions, a possible effect of levosimendan on PDE3 activity and/or intracellular calcium remains very low on mitochondrial activity and insignificant on integrated cardiac energetics. Thus, levosimendan inotropic effect on guinea pig heart depends almost entirely on the calcium-sensitizing properties leading to myofilament activation and the concomitant activation of energy supply by the decrease in PCr, therefore improving energetic efficiency of contraction.


1970 ◽  
Vol 48 (12) ◽  
pp. 801-812 ◽  
Author(s):  
K. Prasad ◽  
John C. Callaghan

Effects of glucose, anoxia, iodoacetate, and 2,4-dinitrophenol on the ouabin-induced changes in the simultaneously recorded transmembrane action potential and contraction of 72 human papillary muscle strips obtained from 36 patients undergoing corrective open heart surgery were investigated. Ouabain (10−8M, 10−9M, 10−10M) produced a shortening of the action potential duration (APD) and an increase in the force of contraction in the muscle. Non-oxygenated glucose-free solution, iodoacetate (10−5M), and 2,4-dinitrophenol (10−6M) produced partial to complete inhibition of the positive inotropic effects of ouabain (10−8M or 10−9M) in the papillary muscles. The shortening of the APD produced by ouabain was further enhanced in the presence of the above metabolic inhibitors. As the glucose level was raised (0, 5, 10, 20, 30 mM), anoxic papillary muscles responded to ouabain by a progressive increase in the force of contraction and a parallel increase in the APD. Glucose (30 mM) was effective in restoring the positive inotropic effects of ouabain in DNP-poisoned muscle while it was ineffective in doing so in the muscle poisoned with both IAA and DNP. These results indicate the requirement of energy for the positive inotropic effects of ouabain in cardiac muscle.


1965 ◽  
Vol 48 (5) ◽  
pp. 887-899 ◽  
Author(s):  
Don P. MacLeod ◽  
E. E. Daniel

The response of the cat papillary muscle to anoxia has been found to alter depending on the glucose concentration in the medium. At a glucose concentration of 5 mM anoxia caused a marked reduction in force of contraction and action potential duration within 20 minutes. At a glucose concentration of 50 mM anoxia induced similar changes in the force of contraction but little or no change in action potential duration. Elevation of glucose concentration during an anoxic interval reversed the anoxia-induced changes in action potential but had little effect on force of contraction. This effect of glucose could be partially duplicated by xylose and 2-deoxyglucose and in addition, 2-deoxyglucose has been found to prevent the effect of subsequently added glucose. These sugars appear to be transported by a system responsible for glucose transport but are not metabolized to any extent. It would appear therefore that transport of glucose is in some way related to transport of potassium as increased potassium permeability is thought by many to be responsible for anoxia-induced changes in action potential duration.


1997 ◽  
Vol 73 ◽  
pp. 47
Author(s):  
Shigeki Miyamoto ◽  
Hiroshi Ozaki ◽  
Masatoshi Hori ◽  
Masao Endoh ◽  
Hideaki Karaki

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