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Measuring the Acute Physiological Effects of Leptin in the Carotid Body

Pye, Richard Laurence

Abstract Details

2015, Doctor of Philosophy (PhD), Wright State University, Biomedical Sciences PhD.
Obesity is the healthcare crisis of our generation. Circulating levels of the adipokine leptin are proportional to adiposity and in addition to its role as a satiety factor leptin has been shown to have a host of pleiotropic effects. Among these effects is its role as a respiratory stimulant where it has been shown to have both whole body and central stimulatory effects on breathing. Porzionato et al. (2011) showed that leptin and leptin receptors are selectively expressed in the chemosensing type I cells of the carotid body. Carotid bodies are small chemosensitive organs that act as the primary peripheral oxygen sensors, sitting bilaterally in the bifurcations of the left and right common carotid arteries. In addition to sampling blood gasses on their way to the brain they play a role in setting central sensitivity to CO2 and play a key role in sleep apnea induced hypertension. Whilst leptin receptors in the carotid body have been shown to be functional, the acute physiological effects of leptin on type I cell function has not been assessed. Work presented here shows that acutely administered leptin: (1) increases intracellular Ca2+ that is dependent on extracellular Ca2+ and PI3Kinase in type I cells; (2) increases membrane conductance of type I cells in a BKCa dependent manner, without altering membrane potential – suggesting that BKCa channels are not open at resting membrane potential in CB type I cells; (3) does not increase acid or hypoxia induced membrane depolarization in isolated CB type I cells, but does increase baseline activity and the size of hypoxic responses in arterially perfused ex-vivo carotid body preparations. This work demonstrates that leptin affects CB function acutely. Investigating the effects of chronic hyperleptinemia on carotid body activity would appear to be warranted based on these findings.
Christopher Wyatt, Ph.D. (Advisor)
Thomas Brown, Ph.D. (Committee Member)
Madhavi Kadakia, Ph.D. (Committee Member)
Robert Putnam, Ph.D. (Committee Member)
Nicholas Reo, Ph.D. (Committee Member)
180 p.

Recommended Citations

Citations

  • Pye, R. L. (2015). Measuring the Acute Physiological Effects of Leptin in the Carotid Body [Doctoral dissertation, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1449583350

    APA Style (7th edition)

  • Pye, Richard. Measuring the Acute Physiological Effects of Leptin in the Carotid Body. 2015. Wright State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1449583350.

    MLA Style (8th edition)

  • Pye, Richard. "Measuring the Acute Physiological Effects of Leptin in the Carotid Body." Doctoral dissertation, Wright State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=wright1449583350

    Chicago Manual of Style (17th edition)