Effect of chlordecone (Kepone) on calcium transport mechanisms in rat heart sarcoplasmic reticulum.
Previous studies from our laboratory have indicated that chlordecone (Kepone CD), an organochlorine insecticide, inhibited cardiac sodium pump activity and catecholamine uptake suggesting that CD may interfere with cardiac function. Sarcoplasmic reticulum (SR) calcium pump has an important role in myocardial contraction and relaxation, besides Na+ transport. Since CD interferes with cardiac Na+ ion translocases, we have studied CD effects on cardiac SR calcium pump activity. Experiments were carried out both in vitro and in vivo. SR was isolated from heart ventricles of male Sprague-Dawley rats. Cardiac SR Ca2(+)-ATPase. 45Ca-uptake and cAMP as well as calmodulin (CaM) dependent protein phosphorylation were measured. Ca2(+)-ATPase was differentiated into low affinity and high affinity forms by measuring the activity using 50 and 0.7 microM free Ca2(+)-respectively. CD in vitro inhibited 45Ca-uptake by SR in a concentration dependent manner with an IC50 value of 7 microM and SR 45Ca-uptake was totally inhibited at 20-30 microM CD. In agreement with this, both high affinity and low affinity Ca2(+)-ATPases, which are involved in Ca2+ transport across membranes, were also inhibited by CD in a concentration dependent manner with IC50 values of 0.7 and 3.2 microM respectively. Both Ca2(+)-ATPase and 45Ca-uptake by cardiac SR were significantly lower in rats treated with CD (25, 50 or 75 mg/kg) when compared to control rats. cAMP as well as CaM significantly elevated the 32P-binding to SR proteins in vitro to about 70-80%. In the presence of CD, this 32P-binding was reduced, however, not concentration dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neurology, University of Mississippi Medical Center, Jackson 39216.
P R
PR
Kodavanti
J A
JA
Cameron
P R
PR
Yallapragada
D
D
Desaiah
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D007631:Chlordecone / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D009124:Muscle Proteins; D007631:Chlordecone; D002118:Calcium