Work in the basic research laboratory of Dr. Victor Ruiz-Velasco is focused on the study of mechanisms by which second messengers, particularly G proteins, modulate voltage-dependent N-type Ca2+ channels. Several electrophysiological, biochemical and molecular approaches are employed to help us understand these signaling pathways. Dissociated stellate ganglion neurons are used as our model system (Neurosci. Lett. 363: 252-256, 2004). This ganglion provides the main sympathetic input to the heart.
Presently, the main focus of the laboratory is to study the neuronal signaling pathways by which the endogenous opioid peptide nociceptin regulates stellate ganglion neuron excitability (J. Pharm. Exp. Ther. 314: 987-994, 2005). Nociceptin activates the opioid receptor-like 1 (ORL1) G protein-coupled receptor. Currently, we are trying to determine the specific G-protein components and regulators of G-protein signaling (RGS) that couple ORL1 receptors with N-type Ca2+ channels. In addition, we are investigating whether ORL1 receptors are capable of dimerizing with each other and with other “classical” opioid receptors. Accordingly, the goal of this research is to understand the signaling events associated with nociceptin-activated ORL1 receptors and regulation of heart rate and contractility.