Protection from Cerebral Embolic Events During Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) has been a major advancement in the treatment of high-risk patients with severe aortic stenosis. One of the primary concerns in applying this procedure to a broader patient population is the risk of embolic stroke. Cerebral emboli have been shown to originate from atheromatous plaques within the aorta and from the degenerate stenotic aortic valve itself.

Sympathetic stimulation of adult cardiomyocytes requires association of AKAP5 with a subpopulation of L-type calcium channels.

Rationale: Sympathetic stimulation of the heart increases the force of contraction and rate of ventricular relaxation by triggering protein kinase (PK)A-dependent phosphorylation of proteins that regulate intracellular calcium. We hypothesized that scaffolding of cAMP signaling complexes by AKAP5 is required for efficient sympathetic stimulation of calcium transients.

Objective: We examined the function of AKAP5 in the β-adrenergic signaling cascade.

NFATc3-dependent loss of I(to) gradient across the left ventricular wall during chronic beta adrenergic stimulation.

In heart, pore-forming Kv4 alpha channel subunits underlie the K(+) transient outward current (I(to)). Expression of Kv4 is greater in left ventricular epicardial (EPI) than in endocardial (ENDO) cells, resulting in larger I(to) in EPI than in ENDO cells. In adult ventricular myocytes, the transcription factor NFATc3 suppresses Kv4 expression.

Functional role of amino terminus in ClC-3 chloride channel regulation by phosphorylation and cell volume.

Aim: This study investigated the functional role of the ClC-3 amino-terminus in channel regulation in response to changes in cell volume.

Methods: Wild-type sClC-3 tagged with a green fluorescence protein (GFP) at the C-terminus was used as a template to construct a number of deletion mutants which were functionally expressed in NIH-3T3 cells. Whole cell and single channel patch-clamp electrophysiology was used to determine the functional properties of heterologously expressed channels.