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.
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