CHAPTER 9 



Action of electrolytes and drugs on the contractile 

 mechanism of the cardiac muscle cell 



EDWARD LEO X A R D 

 STEPHEN HAJDU 



National Heart Institute, National Institutes of Health, Bethesda, Maryland 



CHAPTER CONTENTS 



Contractility 



Work Capacity and Lengtli-Tension Curves 



Isotonic Measurements 



Velocity of Shortening 



Active State 



Efficiency 



Applications to Cardiac Muscle 

 Sodium and Potassium 



Distribution of Sodium and Potassium in Muscle 



Ion Concentrations and Bioelectrical Potentials 



Potassium and Cardiac Excitability 



Effects of Sodium and Potassium on Contractility 

 Other Alkali Metal Ions 



Lithium 



Rubidium 

 Calcium 



Effect of Calcium on Contractility 



Calcium and the Electrical Properties of Excitable Tissue 



Chemical State of Calcium in Living Tissue 



Movements of Calcium In and Out of Cells 

 Cells at rest 

 Cells during activity 



Locus of Action of Calcium on Contractility 

 Other Alkali Earth Metal Ions 



Magnesium 



Barium 

 Effect of Stimulation Frequency on Contractile Force 



Historical Note and Definitions 



The Bowditch Staircase 



Reverse Staircase 



Postextrasystolic Potentiation 

 Quinidine 



General 



Electrical Changes 



Effect of Quinidine on Ionic Concentration and Fluxes in 

 Muscle 

 Ionic concentrations 



Ionic fluxes 



Effects of external potassium concentration on quinidine 

 action 



Discussion 

 Effect of Quinidine on Metabolism 

 Veratrum Alkaloids 



Summary of General Effects on Heart 

 Electrophysiological Details 



Effect on excitability and related phenomena 



Membrane potential changes 

 Effects on Contractility and Ion Movements 



Contractility 



Potassium movements 

 Digitalis 



Metabolism 



Action of Glycosides on Muscle Proteins and Models 



Site of Glycoside Action 



Membrane Transport 



Glycoside-induced net potassium loss from muscle 



Mechanism of the potassium loss 



Glycoside-potassium antagonism 



Changes in muscle ionic composition caused by glyco- 

 sides and their relationship to the positive inotropic 

 action of the drug 



Glycosides and calcium 

 Membrane Potential 



THIS CHAPTER is an essay on the cell physiology' of 

 cardiac muscle. It is oriented toward the problem of 

 regulation of muscle contractility, and therefore the 

 focus will be on a number of cations and drugs which 

 provide insight into cellular mechanisms that affect 

 heart muscle contractile force. The study of muscle 

 has a long tradition, and it should be noted that in- 

 vestigators working primarily on cardiac muscle 



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