Inner sarcolemmal leaflet Ca(2+) binding: its role in cardiac Na/Ca exchange.

Abstract:

:A recently completed model of Ca concentration and movements in the cardiac cell diadic cleft space predicts that removal or neutralization of inner sarcolemmal (SL) leaflet anionic Ca-binding sites at the sarcolemmal border of this space will greatly diminish Na/Ca exchange-mediated Ca efflux. The present study tests this prediction using the local anesthetic dibucaine as a probe. It is shown, in isolated SL, that dibucaine competitively displaces Ca specifically from anionic phospholipid headgroups. Dibucaine also displaces Ca from the SL when applied to intact cells. It does not affect the content or release of Ca from sarcoplasmic reticulum (SR) in these cells. This eliminates a primary effect on SR Ca as a contributing factor to dibucaine's effect on Na/Ca exchange-mediated Ca efflux. Measurement of this efflux from whole cells shows a highly significant reduction of 58% (p < 0.001) by 0.5 mM dibucaine. The inhibiting effect of dibucaine on Na/Ca exchange-mediated Ca efflux can be significantly reversed by augmentation of Ca release from SR by caffeine at the time of activation of Na/Ca exchange. This supports the contention that the dibucaine-SL interaction is a competitive one vis-a-vis Ca. The results are supportive of the model in which inner SL leaflet Ca-binding sites account for the delay of Ca diffusion from the diadic cleft, thereby prolonging the time for which [Ca] remains elevated in the cleft. The prolonged increased [Ca] significantly enhances the ability of Na/Ca exchange to remove Ca from the cell during the excitation-contraction cycle.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Wang SY,Peskoff A,Langer GA

doi

10.1016/S0006-3495(96)79792-8

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

2266-74

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(96)79792-8

journal_volume

70

pub_type

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