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Emerging Physiological Significance Of R-Type Calcium Currents, Paul Jensen May 2006

Emerging Physiological Significance Of R-Type Calcium Currents, Paul Jensen

Undergraduate Honors Capstone Projects

R-type channels are voltage dependent calcium channel subtypes. To date, the only variant of the R-type calcium channel that has been isolated and cloned is the Cav2.3 variant, encoded by the gene Cchral (Yamazaki et al., 1998). The channel was named "R-type" because it was initially characterized by its resistance to nifedipine (a blocker of L-type calcium channels), Ω-conotoxin GVIA (an N-type calcium channel blocker) and Ω -Aga IVA (a blocker of P/Q-type calcium channels) (Hille 2001). The Cav2.3 calcium channel is selectively inhibited by the peptide SNX-482, which was isolated from venom of the African …


Regulation Of Cardiac Fibroblast Metalloprotease Secretion, Glen De Guzman May 2006

Regulation Of Cardiac Fibroblast Metalloprotease Secretion, Glen De Guzman

Undergraduate Honors Capstone Projects

Matrix metalloproteases (MMPs) are proteolytic enzymes secreted by cardiac fibroblasts. Altered expression of MMPs plays an important role in congestive heart failure and other cardiovascular diseases1,2. Emerging evidence has led us to consider the role of phosphatidylinositol 4-kinase (PtdIns 4-kinase) in regulating MMP secretion in cardiac fibroblast cells3-7. PtdIns 4-kinase is a lipid kinase involved in various cellular processes including protein secretion. This project was designed to test the hypothesis that PtdIns 4-kinase controls MMP secretion. Techniques such as cardiac cell culture, transfection, and in-gel zymography were used for this experiment. Results demonstrated that PtdIns 4-kinase …


Modulation Of Fast And Slow Inactivation In Two Cardiac Nav Channel Isoforms By Sdz 211-939, Tyce Jeffrey Kearl May 2006

Modulation Of Fast And Slow Inactivation In Two Cardiac Nav Channel Isoforms By Sdz 211-939, Tyce Jeffrey Kearl

Undergraduate Honors Capstone Projects

Here we report a hitherto unknown effect of a synthetic inactivation inhibitor on inactivation in cardiac sodium channels (Nav1.5) from two different species: human and bovine. SDZ 211-93 9 stabilized the slow inactivated-state in both channels as seen by an increased steady-state probability of slow inactivation. SDZ also destabilized the fast-inactivated state and increased the amplitude of persistent currents. SDZ modulated conductance parameters, open-state fast inactivation time constants, and activation kinetics of hNav1.5, but not bNav1.5. These findings will aid future studies designed to elucidate the binding site and molecular mechanisms of inactivation inhibitors …