L-type calcium current and contractility in ventricular myocytes from mice overexpressing the cardiac β2-adrenoceptor

Abstract

Since only spontaneous beating rate but neither basal ICa,L amplitude nor basal contractile activity were elevated, our data fail to reveal evidence for spontaneously active, stimulating beta 2-ARs in left atrium and ventricle. A contractile deficit unrelated to the beta-adrenoceptor pathway is evident in TG4 myocytes and left atria.

Epinephrine Activates Both Gsand GiPathways, but Norepinephrine Activates Only the GsPathway through Human β2-Adrenoceptors Overexpressed in Mouse Heart

“…Transgenic mice were descendents from the TG4 mice at Duke University (Durham, NC) that overexpress human ␤ 2 -adrenoceptors in a heart-specific manner (Milano et al, 1994). Originally, ␤-adrenoceptor density was increased 200-fold, and the overexpression was verified more recently for our TG4 colony (260-to 435-fold overexpression) (Heubach et al, 1999Graf et al, 2001). TG4 mice were propagated in Dresden by breeding TG4 female mice with wild-type C57BL6 male mice until generation F 7 .…”

T-Type and Tetrodotoxin-Sensitive Ca 2+ Currents Coexist in Guinea Pig Ventricular Myocytes and Are Both Blocked by Mibefradil

“…22 Average values for membrane capacitance measured with 5-millisecond depolarizing ramp pulses (from Ϫ55 to Ϫ50 mV) were 195Ϯ6 pF (rat, nϭ29) and 138Ϯ4 pF (guinea pig, nϭ75; meanϮSEM). Series resistance was routinely compensated by 50% to 70%.…”

β adrenergic receptor-mediated atrial specific up-regulation of RGS5

“…In addition to serving as models of cardio pathologies, the study of these animals has also generated insight into the basic physiology of cardiac AR signaling. TG4 mice, which have a 195-fold increase in cardiac h 2 AR levels, are a widely used model (Heubach et al, 1999(Heubach et al, , 2003Milano et al, 1994). The overexpressed h 2 AR are partly constitutively active and, consequently, the heart rate of these animals remains maximal even at rest.…”