We have produced transgenic mice which overexpress cardiac Na(+)-Ca2+ exchange activity. Overexpression has been assessed by Western blot, Northern blot, and immunofluorescence. Functional overexpression was analyzed using membrane vesicles and isolated ventricular myocytes. In whole cell clamped myocytes dialyzed with 0.1-0.2 mM Fura-2, the magnitude of ICa and Ca2+i-transient triggered by ICa...

BACKGROUND In alpha1-AR knockout (alpha1ABKO) mice that lacked cardiac myocyte alpha1-adrenergic receptor (alpha1-AR) binding, aortic constriction induced apoptosis, dilated cardiomyopathy, and death. However, it was unclear whether these effects were attributable to a lack of cardiac myocyte alpha1-ARs and whether the alpha1A, alpha1B, or both subtypes mediated protection. Therefore, we invest...

Phosphodiesterases (PDEs) are critical regulators of cyclic nucleotides in the heart. In ventricular myocytes, the L-type Ca(2+) current (I(Ca,L)) is a major target of regulation by PDEs, particularly members of the PDE2, PDE3 and PDE4 families. Conversely, much less is known about the roles of PDE2, PDE3 and PDE4 in the regulation of action potential (AP) properties and I(Ca,L) in the sinoatri...

In the present study, we examined if and how cardiac ion channels are modified by type 2 diabetes mellitus (T2DM). Subendocardial (Endo) myocytes and subepicardial (Epi) myocytes were isolated from left ventricles of Otsuka-Long-Evans-Tokushima Fatty rats (OLETF) rats, a rat model of T2DM, and Otsuka-Long-Evans-Tokushima (LETO) rats (nondiabetic control rats). Endo and Epi myocytes were used fo...

AIMS Support with left ventricular assist devices (LVAD) improves cardiac performance in patients with end-stage heart failure. In some cases this strategy, combined with pharmacological treatment, has led to a clinical improvement which remained after LVAD explant. This study defines changes in Ca handling at the cellular level in failing left ventricular tissue taken at LVAD implant (LVAD cor...

BACKGROUND Increasing evidence indicates that the rapid component of delayed rectifier potassium current (I(Kr)) is modulated by α- and β-adrenergic stimulation. However, the role and mechanism regulating I(Kr) through β(2)-adrenoreceptor (β-AR) stimulation in heart failure (HF) are unclear. METHODOLOGY/PRINCIPAL FINDINGS In the present study, we investigated the effects of fenoterol, a highl...

Postnatal growth of the mammalian ventricular myocyte is characterized by a brief period of hyperplasia followed by an extensive period of physiological hypertrophy. Using myocytes isolated from both Wistar-Kyoto and spontaneously hypertensive rats from fetus to 10 months old, we analyzed morphological, biochemical, and ploidy changes. Fetal myocytes from both spontaneously hypertensive and Wis...

BACKGROUND The role of androgens in producing cardiac hypertrophy by direct action on cardiac myocytes is uncertain. Accordingly, we tested the hypothesis that cardiac myocytes in adult men and women express an androgen receptor gene and that myocytes respond to androgens by a hypertrophic response. METHODS AND RESULTS We used reverse transcription-polymerase chain reaction methods to demonst...

An increased phospholamban (PLB)-to-sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) ratio has been suggested to contribute to the slowing of relaxation in failing human ventricle. We have used an adenoviral vector carrying the sequence for PLB to increase this ratio in isolated adult rat ventricular myocytes, and we have examined the functional consequences. With use of adenoviral vectors, t...

Depressed contractility of failing myocytes involves a decreased rate of rise of the Ca2+ transient. Synchronization of Ca2+ release from the junctional sarcoplasmic reticulum (SR) is responsible for the rapid rise of the normal Ca2+ transient. This study examined the idea that spatially and temporally dyssynchronous SR Ca2+ release slows the rise of the cytosolic Ca2+ transient in failing feli...