Homozygous overexpression of the Na+-Ca2+ exchanger in mice: evidence for increased transsarcolemmal Ca2+ fluxes.
Mice with homozygous overexpression of the Na+-Ca2+ exchanger (NCX) exhibit threefold levels of NCX expression and an increased Ca2+ extrusion rate. To investigate how Ca2+ homeostasis is maintained in this model, we have characterized Ca2+ influx under these conditions. We find that L-type Ca2+ currents (I(Ca)) inactivate slower due to a reduction of Ca2+-dependent inactivation. Additionally, NCX-overexpressing animals exhibit a prolongation of the action potential (AP). We conclude that transsarcolemmal Ca2+ fluxes in NCX-overexpressing myocytes are balanced by an increase in Ca2+ influx via (a) slowed inactivation of I(Ca) and (b) a prolongation of the AP to compensate for increased Ca2+ efflux.
Pott
Christian
C
Department of Physiology, David Geffen School of Medicine at UCLA, 675 Charles E. Young Dr. South, Los Angeles, CA 90095, USA.
Goldhaber
Joshua I
JI
Philipson
Kenneth D
KD
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006720:Homozygote; D017136:Ion Transport; D051379:Mice; D018408:Patch-Clamp Techniques; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000502:physiology*
D019831:Sodium-Calcium Exchanger; D002118:Calcium