Excitability of afferents evoking the exercise pressor reflex

Project: Research project

Description

DESCRIPTION (provided by applicant): The major goal of this application is to understand the interplay between receptors and channels that control excitability of the thin fiber muscle afferents that evoke the exercise pressor reflex as well as transduce the sensation of pain. The exercise pressor reflex, which arises from the contraction of skeletal muscles, is one of the two neural mechanisms that evoke the cardiovascular adjustments to exercise. These adjustments, which serve to support the ability of skeletal muscles to contract by increasing blood flow and oxygen to exercising muscles, include reflex increases in arterial blood pressure, cardiac output and ventilation. With respect to thin fiber muscle afferents, we propose to combine the power of the in vitro whole-cell patch- clamp technique, which will determine the mechanisms of afferent excitability, with the physiological insights provided by in vivo electrophysiology, which will determine how these mechanisms translate into increased excitability. For in vitro experiments, muscle afferents will be identified by retrograde labeling DRG neurons with DiI that has been injected into the triceps surae muscles. Particular attention will be paid to afferents that have tetradotoxin resistant channels, which will identify them as group IV muscle afferents. For in vivo experiments, thin fiber triceps surae muscle afferents will be identified by their conduction velocities and their receptive fields. In both in vitro and in vivo experiments, particular attention will be paid to the effects two peptides, namely bradykinin and DAMGO, on the membrane and discharge properties of the afferents. The former peptide is expected to be stimulatory and to act on B2 receptors, whereas the latter peptide, which is a
StatusActive
Effective start/end date4/1/103/31/20

Funding

  • National Institutes of Health: $643,914.00
  • National Institutes of Health: $429,642.00
  • National Institutes of Health: $474,681.00
  • National Institutes of Health: $425,726.00
  • National Institutes of Health: $618,375.00
  • National Institutes of Health: $28,202.00
  • National Institutes of Health: $612,584.00
  • National Institutes of Health: $417,211.00
  • National Institutes of Health: $650,821.00
  • National Institutes of Health: $434,998.00
  • National Institutes of Health: $639,830.00

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Reflex
Muscles
Social Adjustment
Skeletal Muscle
Aptitude
Electrophysiology
Diagnosis-Related Groups
Patch-Clamp Techniques
Peptides
Cardiac Output
Ventilation
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Oxygen
Neurons
Pain
Tetrodotoxin
Bradykinin
Afferent Neurons
Opioid Receptors
Arterial Pressure