• Somers, Virend (PI)
  • Sanford, L. Phillip (PI)
  • Davisson, Robin L. (PI)
  • Talman, William (PI)
  • Woolson, Robert (PI)
  • Farley, Donna (PI)
  • Lewis, Stephen (PI)
  • Robillard, Jean (PI)
  • Sharma, Ram (PI)
  • Heistad, Donald (PI)
  • Felder, Robert (PI)
  • Johnson, Alan (PI)
  • Abboud, Francois (PI)
  • Abboud, Francois (PI)
  • Marcus, Melvin (PI)
  • Thames, Marc (PI)
  • Hermsmeyer, Kent (PI)
  • Di Bona, Gerald (PI)
  • Meyerholz, David (PI)
  • Clark, Edward (PI)
  • Brody, Michael (PI)
  • Lachenbruch, Peter (PI)
  • Kerber, Richard (PI)
  • Mirro, Michael (PI)
  • Jennings, Michael (PI)
  • Rubenstein, Peter (PI)
  • Steinmetz, Philip (PI)
  • Schmid, Phillip (PI)
  • Swenson, Charles (PI)
  • Mark, Allyn (PI)
  • Sanford, L. Phillip (PI)
  • Lawton, William (PI)
  • Stellwagen, Earle (PI)
  • Stokes, John (PI)
  • Marvin, William (PI)
  • Talman, William (PI)
  • Woolson, Robert (PI)
  • Lewis, Stephen (PI)
  • Farley, Donna (PI)
  • Sharma, Ram (PI)
  • Heistad, Donald (PI)
  • Chapleau, Mark (PI)
  • Russo, Andrew (PI)
  • Bhalla, Ramesh (PI)
  • Haynes, William (PI)
  • Felder, Robert (PI)
  • Davisson, Robin L. (PI)
  • Davidson, Beverly (PI)
  • Yang, Baoli (PI)
  • Sigmund, Curt Daniel (PI)
  • Chapleau, Mark (PI)
  • Haynes, William (PI)
  • Johnson, Alan (PI)
  • Welsh, Michael John (PI)
  • Davisson, Robin L. (PI)

Project: Research project

Project Details


The arterial baroreceptors are sensory endings restricted to the carotid
sinus and aortic arch but with powerful regulatory influences. They
transduce arterial pressure signals into neurohumoral regulation of
cardiovascular structure and homeostasis. Despite a large amount of
information on the determinants of activation of baroreceptor (BR) nerves,
the molecular, cellular and functional determinants of mechanoelectrical
transduction at their sensory nerve endings are largely unknown. Project
IV of this PPG addresses the neurobiology of mechanosensation. This
Project (IV.A.1) which was initiated four years ago, as focused on 1) the
identification of BR neurons in the nodose ganglion; 2) culturing them in
vitro; 3) the development of a quantitative system for their mechanical
activation; and 4) the definition of their responses with measurements of
whole cell membrane currents, single-channel openings [Ca2+]i. A
functional correlate of the cellular mechanisms was sought by measurements
of carotid sinus nerve activity in vivo. Based on very exciting
preliminary studies, we now propose to test the hypothesis that the
ENaC/degenerin family of proteins represent ionic channel responsible for
mechanoelectrical transduction in BR neurons. This hypothesis gains a
strong rationale from the discovery of a genetic link between touch
sensation in C. Elegans and the evidence of mechanical activation of
ENaC/degenerin channels. In preliminary studies we found that 1) the
subunits of ENAC/degenerin, gamma ENaC; beta ENaC and BNC1 (recently
cloned from brain), are expressed in the aortic arch adventitia in the
nodose ganglia where the BR nerve terminals and BR neurons are located,
respectively; 2) the activity of BNC1a (transfected into oocytes) is
blocked by Gd3+, a known blocker of mechanosensory channels; and 3) the
rise in [Ca2+]i in BR neurons during mechanical stimulation is blocked by
amiloride, a known blocker of the ENaC/degenerin channels. Our aims are:
first, to identify ENaC/degenerin ENaC/degenerin channels; and third, to
attempt to disrupt the BR responses to mechanical stimulation at the
cellular, organ and whole animal level by transfection of dominant-
negatives of ENaC/degenerin family.

The uniqueness of the project is in the joining of two leading
laboratories, with expertise in neurobiology of autonomic control (Abboud)
and in the molecular biology of ion channels (Welsh). With the added
support of excellent cores in imaging, transgenic animals, and gene
transfer, the promise of successful pursuit of this problem is
Effective start/end date12/1/765/31/19


  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute


  • Medicine(all)


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