The objective of this project is to quantify the cellular adaptations in carotid body function occurring with in vivo acclimatization to chronic hypoxia (stimulating high altitude) and with combined chronic hypoxia and hypercapnia (simulating chronic lung disease). The carotid body is the primary source of the hypoxic ventilatory drive, but very little is known about the electrophysiological adaptations of the carotid body to chronic hypoxia. Patch clamp techniques will be used to record currents associated with potassium, sodium and calcium ion channels in glomus cells isolated from control and acclimatized rats. We will test for changes in glomus cell ion channel activity and membrane potential associated with acclimatization to O2 and Co2 stimuli. To determine the specificity of measured adaptations to the carotid bogy, we will compare acclimatization responses in glomus cells to change observed in freshly isolated adrenal chromaffin and cultured PC12 cells exposed tot he same treatments. The effects of hypoxic acclimatization on nitric oxide neuromodulation of carotid body function and glomus cell ion channel activity will be quantified. We will determine whether the stimulation of carotid body function by glutamate and inhibition by arginine and lysine is exerted through action on membrane receptors, or through direct physicochemical properties of the amino acids, and whether the modulation is affected by hypoxic acclimatization. We will also study the role of intracellular glomus cell calcium stores on chemoreception using blockers and agonists of ryanodine and inositol triphosphate receptors, before and after acclimatization. These studies will help define the physiological basis for carotid body adaptation to chronic hypoxia in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL017731-23
Application #
6241555
Study Section
Project Start
1997-05-01
Project End
1998-04-30
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
23
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Richardson, Russell S; Wary, Claire; Wray, D Walter et al. (2015) MRS Evidence of Adequate O? Supply in Human Skeletal Muscle at the Onset of Exercise. Med Sci Sports Exerc 47:2299-307
Esposito, F; Wagner, P D; Richardson, R S (2015) Incremental large and small muscle mass exercise in patients with heart failure: evidence of preserved peripheral haemodynamics and metabolism. Acta Physiol (Oxf) 213:688-99
Olfert, I Mark; Malek, Moh H; Eagan, Tomas M L et al. (2014) Inflammatory cytokine response to exercise in alpha-1-antitrypsin deficient COPD patients 'on' or 'off' augmentation therapy. BMC Pulm Med 14:106
Tang, Kechun; Murano, George; Wagner, Harrieth et al. (2013) Impaired exercise capacity and skeletal muscle function in a mouse model of pulmonary inflammation. J Appl Physiol 114:1340-50
Poole, David C; Copp, Steven W; Ferguson, Scott K et al. (2013) Skeletal muscle capillary function: contemporary observations and novel hypotheses. Exp Physiol 98:1645-58
Koga, S; Wüst, R C I; Walsh, B et al. (2013) Increasing temperature speeds intracellular PO2 kinetics during contractions in single Xenopus skeletal muscle fibers. Am J Physiol Regul Integr Comp Physiol 304:R59-66
Breen, Ellen C; Malloy, Jaret L; Tang, Kechun et al. (2013) Impaired pulmonary defense against Pseudomonas aeruginosa in VEGF gene inactivated mouse lung. J Cell Physiol 228:371-9
Wray, D Walter; Nishiyama, Steven K; Donato, Anthony J et al. (2011) The paradox of oxidative stress and exercise with advancing age. Exerc Sport Sci Rev 39:68-76
Esposito, Fabio; Mathieu-Costello, Odile; Entin, Pauline L et al. (2010) The skeletal muscle VEGF mRNA response to acute exercise in patients with chronic heart failure. Growth Factors 28:139-47
Wray, D Walter; Nishiyama, Steve K; Donato, Anthony J et al. (2010) Human vascular aging: limb-specific lessons. Exerc Sport Sci Rev 38:177-85

Showing the most recent 10 out of 382 publications