Date of Award

5-2006

Degree Type

Thesis

Degree Name

Departmental Honors

Department

Biology

Abstract

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 tarantula Hysterocrates gigas (Newcomb et al., 1998). R-type calcium currents are typically characterized by high voltage activation and rapid kinetics of deactivation (Foehring et al., 2004). Recent studies have begun to show the channel's physiological significance. Several pathophysiological states and diseases have been linked to abnormal R-type calcium currents. Recently Cav2.3 has been identified as a regulator of physiological changes following subarachnoid hemorrhage (SAV) (Ishiguro et al., 2005), blood insulin regulation (Jing et al., 2005), juvenile myoclonic epilepsy (Suzuki et al. 2004), and regulation of synaptic transmission (Cohen et al., 2004). Mechanisms of the channel's regulation, reasons for its association with pathophysiological states, and a pharmacological inhibitor that is effective at therapeutic doses are still being investigated. This thesis will review many of the recent findings about the physiological effects of R-type calcium channels, with special emphasis given to the possible relationship between these channels and epilepsy. It will then present original research regarding the effects of the novel anti-epileptic drug topiramate on R-type calcium channels.

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Faculty Mentor

Brett Adams

Departmental Honors Advisor

Kim Sullivan

Capstone Committee Member

Katarina Stroffekova