Increased exchange current but normal Ca2+ transport via Na+-Ca2+ exchange during cardiac hypertrophy after myocardial infarction.
Hypertrophied and failing cardiac myocytes generally show alterations in intracellular Ca2+ handling associated with changes in the contractile function and arrhythmogenicity. The cardiac Na+-Ca2+ exchange (NCX) is an important mechanism for Ca2+ extrusion and cell relaxation. Its possible involvement in changes of excitation-contraction coupling (EC-coupling) with disease remains uncertain. We analyzed the NCX function in rat ventricular myocytes 5 to 6 months after experimental myocardial infarction (PMI) produced by left coronary artery ligation and from sham-operated (SO) hearts. Caged Ca2+ was dialyzed into the cytoplasm via a patch-clamp pipette and Ca2+ was released by flash photolysis to activate NCX and measure the associated currents (I(NaCa)), whereas [Ca2+]i changes were simultaneously recorded with a confocal microscope. I(NaCa) density normalized to the [Ca2+]i jumps was 2.6-fold higher in myocytes from PMI rats. The level of total NCX protein expression in PMI myocytes was also increased. Interestingly, although the I(NaCa) density in PMI cells was larger, PMI and SO myocytes presented virtually identical Ca2+ transport via the NCX. This discrepancy was explained by a reduced surface/volume ratio (34.8%) observed in PMI cells. We conclude that the increase in NCX density may be a mechanism to maintain the required Ca2+ extrusion from a larger cell to allow adequate relaxation.
Department of Physiology, University of Bern, Bern, Switzerland.
Ana Maria
AM
Gómez
Beat
B
Schwaller
Hartmut
H
Porzig
Guy
G
Vassort
Ernst
E
Niggli
Marcel
M
Egger
D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism*; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002469:Cell Separation; D004195:Disease Models, Animal; D018450:Disease Progression; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D017136:Ion Transport; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D018408:Patch-Clamp Techniques; D010782:Photolysis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling
D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D002118:Calcium