PROBLEM #1 INTRODUCTION Cardiac muscle contractile strength can be changed by al

Question

PROBLEM #1 INTRODUCTION

Cardiac muscle contractile strength can be changed by altering its inotropic state (IS). An increase in IS increases contractile activity without requiring a change in muscle fiber length. This mechanism is absent in skeletal muscle.

PROBLEM #1: Digitalis (ouabain) is a drug used to counteract the effects of cardiac failure. In heart failure, one or both ventricles are incapable of developing a normal contractile force or producing a normal stroke volume without an increase in end diastolic filling. In such situations, digitalis increases the inotropic state (contractility) of heart muscle. Digitalis acts by inhibiting the Na+/K+ pump. (By the way, the Na+/K+ pump located in cardiac myocytes has a digitalis-binding site not found on Na+/K+ pumps outside of the heart. This is how digitalis can affect the Na+/K+ in the heart but not elsewhere in the body.)

http://ajpheart.physiology.org/content/289/5/H1781.long

http://www.cvpharmacology.com/cardiostimulatory/digitalis.htm

1. What effect will treatment with digitalis have on the distribution of ions across the membrane of cardiac muscle cells?

2. The cardiac muscle membrane contains a secondary active transporter, a Na+Ca2+ exchanger. This countertransporter is one of the mechanisms that maintains a low cytosolic Ca2+ concentration during diastole. It uses the energy content in the trans-sarcolemmal Na+ electrochemical gradient to transport 3 Na+ into the cell for each Ca2+ it extrudes from the cell. Explain how the action of digitalis interacts with the action of the transporter to increase the force of contraction of the myocardium.

Explanation / Answer

Answer 1- Digitalis acts on cardiac muscle by inhibiting sodium - potassium ATPase which acts on cell membrane level. The function of sodium potassium ATPase is outward movement of sodium and inward movement of potassium from the cell. Thus by inhibiting this enzyme, digitalis causes increase in concentration of sodium within the cells. This results in decrease activity of sodium calcium exchanger. Thus resulting in high level of calcium within the cells. This explains that digitalis causes increased concentration of sodium and calcium within the cell.

Answer 2- The answer 1 explains how digitalis increases the concentration of intracellular calcium by decreasing activity of sodium - calcium exchanger. Thus by increasing concentration of intracellular calcium, more calcium is available for intracellular proteins. And we know that protein causes contraction. So by using these calcium, more contraction will take place. Thus digitalis causes increase in force of contraction.

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