NA-CA2+ EXCHANGE AND SARCOPLASMIC RETICULAR CA2+ REGULATION IN VENTRICULAR MYOCYTES FROM TRANSGENIC MICE OVEREXPRESSING THE NA+-CA2+ EXCHANGER()

Citation
Cmn. Terracciano et al., NA-CA2+ EXCHANGE AND SARCOPLASMIC RETICULAR CA2+ REGULATION IN VENTRICULAR MYOCYTES FROM TRANSGENIC MICE OVEREXPRESSING THE NA+-CA2+ EXCHANGER(), Journal of physiology, 512(3), 1998, pp. 651-667
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
Journal title
ISSN journal
0022-3751
Volume
512
Issue
3
Year of publication
1998
Pages
651 - 667
Database
ISI
SICI code
0022-3751(1998)512:3<651:NEASRC>2.0.ZU;2-J
Abstract
1. The contribution of the sarcoplasmic reticulum (SR) and Na+-Ca2+ ex changer to intracellular Ca2+ regulation in mouse cardiac myocytes was investigated by measuring contraction after variable rest intervals, rapid cooling contractures (RCCs) and fast application of caffeine. Th e results obtained showed differences from other species in the roles played by the SR and the Na+-Ca2+ exchanger. They suggest that in mous e ventricular myocytes there is significant Ca2+ entry via the exchang er during rest and during the latter part of the Ca2+ transient. 2. In cardiac myocytes isolated from transgenic mice overexpressing the car diac Na+-Ca2+ exchanger the time to peak and relaxation of twitches an d RCCs were faster than in control littermates. The decline of Ca2+, a ssessed by indo-1, fluorescence, was faster in transgenic myocytes eve n in the absence of Na+ and Ca2+ in the superfusing solution. This sug gests that SR Ca2+ uptake is faster in these myocytes. However, no dif ference in the expression of SERCA2a, phospholamban or calsequestrin m easured with Western blotting could be found in the two groups. 3. We measured SR Ca2+ content by integrating the caffeine-induced transient inward current. The amount of Ca2+ stored in the SR of transgenic mou se myocytes was 69% greater than in non-transgenic littermates. The in creased SR Ca2+ content may be responsible for the faster rate of SR C a2+ release and uptake in cells from transgenic mice. 4. We performed experiments to assess whether the reversal potential of the Na+-Ca2+ e xchanger (ENa-Ca) was different in transgenic cardiac cells. We measur ed a Ni2+-sensitive current elicited by voltage ramps in non-dialysed myocytes. The current-voltage relationship showed no difference in the reversal potential of the Na+-Ca2+ exchanger in transgenic and contro l myocytes. This suggests that the effects on the SR Ca2+ content in t ransgenic cardiac myocytes can be ascribed to the overexpression of th e exchanger and are not secondary to changes in intracellular diastoli c Ca2+ and Na+.