The role of the Cav3.1 subunit of the T-type calcium channel in the heart after injury using a loss-of-function model

Temple Univ Of The Commonwealth, Philadelphia PA

Investigators

Abstract

? DESCRIPTION (provided by applicant): T-type calcium channels are highly expressed throughout the heart during development, but their expression is limited to pacemaker cells after birth. After an injury to the heart, such as MI, these channels are re-expressed in the adult ventricular myocytes. Calcium influx through these channels has been linked to increased proliferation in a number of cell types. The re-expression of these channels may be serving a beneficial purpose after MI. We will determine if loss of the Cav3.1 subunit of the T-Type calcium channel, using a global knockout model, alters the structural, functional, and molecular adaptions occurring in the myocardium after MI. The structural changes occurring after MI in wild type and Cav 3.1 knockout mice will be assessed using echocardiography and histology. Functional changes will be assessed via echocardiography, hemodynamics, electrocardiogram, and electrophysiology. Molecular changes will be assessed using qRT-PCR and western blot. We will also determine how loss of Cav3.1 expression alters the properties of resident cardiac stem cells by isolating cardiac stem cells and growing them in culture. These cells will be characterized by their surface marker expression, morphology, proliferation rate, rate of senescence, percent of apoptosis, and paracrine factor secretion in comparison to WT cells. In-vivo studies will explore the effects of Cav3.1 KO on post MI angiogenesis, since CDCs are known to generate new blood vessels Finally, we will determine if loss of Cav3.1 expression in bone marrow derived inflammatory cells that infiltrate the heart after MI contributes to altered post MI remodeling via bone marrow transplantation of Cav3.1 KO bone marrow into wild type mice.