Discoordinate regulation of isoforms of Na,K-ATPase and myosin heavy chain in the hypothyroid postnatal rat heart and skeletal muscle.

K J Sweadner,K M Mcgrail,B A Khaw

doi:10.1016/s0021-9258(18)48350-0

Abstract

During postnatal life, many contractile and electrophysiological properties of the rat heart undergo changes. Among the changes is a switch in the expression of Na,K-ATPase catalytic subunit isoforms. Thyroid hormone has been postulated to play an important role in the postnatal transformation of the heart, and its effect on myosin heavy chain isoform gene transcription is well documented. To test whether it controls Na,K-ATPase gene switching in vivo, we made neonatal rats hypothyroid by maternal treatment with methimazole. The expression of Na,K-ATPase catalytic subunit isoforms in cardiac and skeletal muscle membranes was measured with specific antibodies at time points from birth to 4 weeks of age. Postnatal changes in Na,K-ATPase isoform expression in cardiac ventricle and hind limb skeletal muscle were similar in control and hypothyroid animals. In the same hypothyroid animals, the postnatal switch from the V3 (beta) isoform of myosin heavy chain to the V1 (alpha) isoform was blocked. The conclusion is that thyroid hormone may have a modulatory role in Na,K-ATPase gene expression, but it is not the developmental signal that dominates gene switching.

Highlights

IntroductionMany contractile and electrophysiological properties of the rat heart undergo changes
During postnatal life, many contractile and electrophysiological properties of the rat heart undergo changes
Ng et al [44] showed that two electrophoretically different a subunits in ferretheart were differentially affected in this species, the higher affinity and slower migrating a(+) form was unaffected, and the a form was increased by thyroid hormone administration in the heart, but noint the kidney

Summary

Introduction

Many contractile and electrophysiological properties of the rat heart undergo changes. Thyroid hormone has been postulated to play an important role in the postnatal transformation of the heart, and its effect on myosin heavy chain isoform gene transcription is well documented. To test whether it controls Na,K-ATPase gene switching in uiuo, we made neonatal rats hypothyroidby maternal treatment with receptorfor thecardiac glycosides, aclass of drugs with inotropic action in the heart. The expression of Na,K-ATPase cata- Postnatal maturation is characterizebdy several important lytic subunit isoforms in cardiac and skeletal muscle changes in the propertieosf cardiac muscle [3].In the rat, the membranes was measured with specific antibodies at time points from birth to 4 weeks of age. Na+:Ca2+ exchange.It has two types of subunits: a catalytic physiological consequence of the switch between a3 and a2 is subunit ( a ) that spans the membrane multiple times and a not known

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Conclusion