METABOTROPIC RECEPTOR MODULATION OF BARORECEPTOR NEURONS

Information concerning the level of blood pressure originates from both
arterial and cardiac baroreceptors. Activation of these receptors results
in the generation of action potentials which ultimately results in the
central release of baroreceptor neurotransmitters and the activation of
central neurons involved in cardiovascular reflex control. In a number of
different animal models, the reflex influences of either the arterial or
cardiac baroreceptors is significantly influenced by activation the other.
Few studies, however, have focused on the cellular mechanisms involved in
these integrated responses. One hypothesized mechanism for baroreceptor afferent integration involves
autoreceptive neurotransmission. Neurotransmitters, known to be released
by baroreceptor neurons (i.e. glutamate) may feedback to modulate their
own release. To gain insight into the possible baroreceptor
neurotransmitter receptor systems which may be involved in baroreceptor
integration, this project will examine the role of the 1-glutamate
metabotropic and 1-AP4 receptors in the regulation of baroreceptor
neuronal activity. The proposed studies will use primary cell culture
techniques in conjunction with patch-clamp methodology and fluorescent
histochemistry to examine the specific ion channels involved in
metabotropic receptOr modulation of baroreceptor neurons. This model takes
advantage of the fact that ion channels and metabotropic receptors present
in the soma of sensory afferents are functionally similar to those present
on the central terminals. Thus, the study of the metabotropic receptor
modulation of baroreceptor somatic ion channels will closely reflect the
nature of this receptor system at the central terminals. The specific aims of this project are: 1) To determine and characterize
the voltage-gated and calcium. activated ionic currents present in cardiac
baroreceptor neurons; 2) To identify the role of glutamate metabotropic
receptors in the regulation of both arterial and cardiac baroreceptor
voltage-gated and calcium-dependent ion currents; and 3) To determine the
effects of l-AP4 receptor activation on voltage-gated and calcium-
activated currents in arterial and cardiac baroreceptor neurons. These studies are expected to yield specific information concerning
neurotransmitter regulation of baroreceptor ion channels and provide a
mechanistic theory as to how peripheral baroreceptor afferents may
modulate their own activity.