Graduation Year

2005

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Pharmacology and Therapeutics

Major Professor

Javier Cuevas, Ph.D.

Co-Major Professor

Lynn Wecker, Ph.D

Keywords

Calcium channel, Potassium channel, Sodium channel

Abstract

Sigma receptors have been implicated in the regulation of the cardiovascular system. Some of the cardiovascular effects of sigma receptors may be through the modulation of autonomic neurons. Studies on the expression and cellular function of sigma receptors in autonomic neurons were conducted in neonatal rat intracardiac (ICG) and superior cervical ganglia (SCG). Individual neurons from SCG and ICG were shown to express transcripts encoding the sigma-1 receptor. The effects of sigma receptors activation on high-voltage-activated Ca2+ channels was studied in isolated neurons of these ganglia. Bath application of sigma receptor agonists depressed peak calcium channel currents in a dose-dependent manner and the rank order potency of haloperidol> ibogaine > (+)-pentazocine > DTG is consistent with the effects being mediated by a sigma-2 receptor. Sigma receptor antagonist, metaphit, blocked DTG-mediated inhibition of Ca2+ current.

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