Tejus
A. Bale
B.S. Stony Brook University, 2006
2nd
Year Graduate Student
Advisor:
Irene C. Solomon, Ph.D.
Department: Pysiology & Biophysics
Graduate Program: Physiology & Biophysics
Abstract:
Title:
Influence of 5-HT2A receptor blockade
on hypercapnic ventilatory response in arterially-perfused adult rat
A number of pathologies
of breathing are postulated to arise from the failure to sense or respond
appropriately to elevated levels of CO2 hypercapnia). Serotonergic
raphe neurons have been identified as putative respiratory CO2
chemosensors, and accumulating evidence suggests that disturbances in
the serotonergic system may underlie these breathing pathologies. The
role of serotonin (5-HT) signaling in the hypercapnic ventilatory response,
however, has yet to be fully characterized. To begin to address this
issue, we examined the effects of 5-HT2A receptor
blockade on the phrenic nerve discharge response to elevated levels
of CO2 in 5 arterially-perfused adult rat preparations. 5-HT2A
receptors were blocked using ketanserin (KTN; 40 µM). Although
perfusion with KTN increased the frequency and decreased the amplitude
of basal phrenic bursts, increasing the CO2 gassing the aCSF
from 5-10% further increased burst frequency by ~26%, produced a small
(~7%) increase in burst amplitude, shifted the time-to-peak activity
to ~20% earlier in the burst, and decreased inspiratory neural network
complexity. Similar effects were observed under control conditions,
but the magnitude of the frequency response was slightly greater and
mediated only by decreases in TE during KTN perfusion. These data suggest
that activation of 5-HT2A receptors may participate
in the hypercapnic ventilatory response. Supported by NS045321.
Publications:
Bale, T.A. and Solomon,
I.C. (2009). Influence of 5-HT2A Receptor Blockade on Phrenic Nerve
Discharge at Three Levels of Extracellular K+ in Arterially-Perfused
Adult Rat Adv Exp Med Biol. 606 (in press).
Bale, T.A. and Solomon,
I.C. (2009). Ketanserin-Induced Blockade of 5-HT2 Receptors Alters Hypercapnic
Respiratory Responses in Arterially-Perfused Adult Rat (in preparation).
