Will imaging assist in the selection of patients with heart failure for an ICD?

Sudden cardiac death remains the leading cause of death in the U.S. A left ventricular ejection fraction (LVEF)<30% to 35% identifies a population of patients at increased risk for sudden cardiac death.

Targeted disruption of the voltage-dependent calcium channel alpha2/delta-1-subunit.

Cardiac L-type voltage-dependent Ca(2+) channels are heteromultimeric polypeptide complexes of alpha(1)-, alpha(2)/delta-, and beta-subunits. The alpha(2)/delta-1-subunit possesses a stereoselective, high-affinity binding site for gabapentin, widely used to treat epilepsy and postherpetic neuralgic pain as well as sleep disorders. Mutations in alpha(2)/delta-subunits of voltage-dependent Ca(2+) channels have been associated with different diseases, including epilepsy.

Electrical remodeling in hearts from a calcium-dependent mouse model of hypertrophy and failure: complex nature of K+ current changes and action potential duration.

Objectives: This study was designed to identify possible electrical remodeling (ER) in transgenic (Tg) mice with over-expressed L-type Ca(2+) channels. Transient outward K(+) current (I(to)) and action potential duration (APD) were studied in 2-, 4-, 8-, and 9- to 12-month-old mice to determine linkage to ventricular remodeling (VR), ER, and heart failure (HF).

Background: Prolongation of APD and reduction in current density of I(to) are thought to be hallmarks of VR and HF.

Mice with cardiac-specific sequestration of the beta-subunit of the L-type calcium channel.

The beta subunit of the L-type voltage-dependent calcium channel modifies the properties of the channel complex by both allosteric modulation of the alpha1 subunit function and by chaperoning the translocation of the alpha1 subunit to the plasma membrane. The goal of this study was to investigate the functional effect of changing the in vivo stoichiometry between the alpha1 and beta subunits by creating a dominant negative expression system in a transgenic mouse model. The high affinity beta subunit-binding domain of the alpha1 subunit was overexpressed in a cardiac-specific manner to act as a beta subunit trap.

Ca(2+) signaling in cardiac myocytes overexpressing the alpha(1) subunit of L-type Ca(2+) channel.

Voltage-gated L-type Ca(2+) channels (LCCs) provide Ca(2+) ingress into cardiac myocytes and play a key role in intracellular Ca(2+) homeostasis and excitation-contraction coupling. We investigated the effects of a constitutive increase of LCC density on Ca(2+) signaling in ventricular myocytes from 4-month-old transgenic (Tg) mice overexpressing the alpha(1) subunit of LCC in the heart. At this age, cells were somewhat hypertrophic as reflected by a 20% increase in cell capacitance relative to those from nontransgenic (Ntg) littermates.