Date of Award
Doctor of Philosophy (PhD)
Colin A. Nurse
The mammalian carotid body is a small chemosensory organ, located at the carotid bifurication which senses blood levels of oxygen, carbon dioxide, and acidity and controls breathing. In response to these chemosensory stimuli nerve impulses emanating from the carotid body are conveyed along the carotid sinus nerve and forward information to the respiratory control centre in the brainstem. The chemosensors in the carotid body were presumed to be the glomus or type I cells, which contain neurotransmitters and receive a direct sensory innervation, although relatively little is known about their physiology. The goals of this thesis were to characterize the electrophysiological properties of glomus cells from the rat carotid body and determine if they are modified by exposure to the chemosensory stimuli. The use of cell cultures of dissociated carotid bodies allowed virtual isolation of glomus cells making them accessible for study by the modern electrophysiological patch clamp/whole-cell technique. This high resolution method is ideally suited for electrophysiological recording from small cells (such as the glomus cells) and allows the measurement of current flow through single ion-channel proteins. Whole-cell recording from glomus cells under voltage clamp revealed the presence of voltage-activated Na⁺, K⁺, and Ca²⁺ currents as well as leakage anion (Cl⁻/HCO₃⁺) channels which were unmasked in physiological bicarbonate/CO₂-containing media. Acute exposure to hypoxia (Po₂≈20-30 Torr) caused a selective suppression of K⁺ currents in glomus cells while chronic exposure (up to 2 weeks) to hypoxia (Po₂≈50 Torr) promoted the selective induction of Na⁺ channels and caused hypertrophy of these cells. Both these effects appear to be mediated via the second messenger cAMP and may account for the increased sensitivity and enlargement of the carotid body following chronic hypoxia. The other chemosensory stimuli, extracellular acidification and hypercapnia, decreased both Na⁺ and K⁺ currents in glomus cells. The effects of both these stimuli were likely mediated via cytoplasmic acidification as directly lowering pHᵢ had similar effects on the membrane currents and carbonic anhydrase activity, which is present in these cells cytoplasm, is known to cause acidification in the presence of CO₂. A discussion of the intrinsic physiological mechanisms of chemotransduction by glomus cells revolves around modulations of the voltage-activated K⁺, and Na⁺ currents during chemosensory stimulation causing alterations in intracellular Ca²⁺ and pH. These changes in Ca²⁺ᵢ and pHᵢ cause neurotransmitter release onto the sensory nerve endings finally leading to increased breathing by a reflex pathway through the respiratory control centre in the brainstem.
Stea, Anthony Jean, "Investigations of chemosensory mechanisms in cultured glomus cells of the rat carotid body using patch clamp/whole-cell recording" (1992). Open Access Dissertations and Theses. Paper 3621.