Type of event:
Audience / Guests:
This seminar will explore recent evidence which suggests that the principal central respiratory chemoreceptors are located within the retrotrapezoid nucleus (RTN) and that RTN neurons are directly sensitive to protons [H(+)]. RTN neurons are glutamatergic. In vitro, their activation by protons requires expression of a proton-activated G protein-coupled receptor (GPR4) and a proton-modulated potassium channel (TASK-2) whose transcripts are undetectable in astrocytes and the rest of the lower brainstem respiratory network. The pH response of RTN neurons is modulated by surrounding astrocytes but genetic deletion of RTN neurons or deletion of both GPR4 and TASK-2 virtually eliminates the central respiratory chemoreflex. Thus, although this reflex is regulated by innumerable brain pathways, it seems to operate predominantly by modulating the discharge rate of RTN neurons, and the activation of RTN neurons by hypercapnia may ultimately derive from their intrinsic pH sensitivity. RTN neurons are also activated by inputs from serotonergic neurons and hypothalamic neurons. The absence of RTN neurons probably underlies the sleep apnea and lack of chemoreflex that characterize congenital central hypoventilation syndrome.
Dr Natasha Kumar completed her PhD at the Department of Physiology (University of Sydney) and joined Macquarie University in 2007 as a postdoctoral fellow with A/Prof Ann Goodchild. This was followed by postdoctoral training at the Department of Pharmacology, University of Virginia (Prof. Douglas Bayliss; 2011-2016). There, her research projects focused on the molecular basis of ion channels and GPCRs that determine intrinsic excitability of brain cells. Currently, she is establishing her independent laboratory at the Department of Pharmacology, UNSW. Her research interests include cellular and physiological mechanisms used by autonomic systems; cardiovascular, respiratory and glucoregulatory.