The long term goals of this work are to understand the cellular mechanisms involved in the hypercapnic response of central chemosensite neurons involved in cardiorespiratory control. Chemosensitive neurons from neonatal rats that have been adapted to chronic hypercapnia, which have reduced ventilatory responses to acute hypercapnia, will be studied. The response of these chemosensitive neurons is presumably mediated by a sustained hypercapnia-induced intracellular acidification that results in increased excitability due to inhibition of K+ channels, resulting in an increased firing rate. Using fluorescence imaging microscopy to study intracellular pH and whole cell patch electrodes to study firing rate in these neurons, the hypothesis will be tested that the reduced ventilatory response to CO2 in rats adapted to chronic hypercapnia is due to an increase in pH regulating membrane transporters (especially Na/H exchangers), that are up-regulated by chronic acidosis. Reduced excitability of these neurons may also be due to altered expression of acid-sensitive ion channels. The findings will be of relevance to pathological conditions that involve chronic hypercapnia, such as heart failure or chronic obstructive pulmonary disease.
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| Kersh, Anna E; Hartzler, Lynn K; Havlin, Kevin et al. (2009) pH regulating transporters in neurons from various chemosensitive brainstem regions in neonatal rats. Am J Physiol Regul Integr Comp Physiol 297:R1409-20 |
| Nichols, Nicole L; Hartzler, Lynn K; Conrad, Susan C et al. (2008) Intrinsic chemosensitivity of individual nucleus tractus solitarius (NTS) and locus coeruleus (LC) neurons from neonatal rats. Adv Exp Med Biol 605:348-52 |
| Hartzler, Lynn K; Dean, Jay B; Putnam, Robert W (2008) The chemosensitive response of neurons from the locus coeruleus (LC) to hypercapnic acidosis with clamped intracellular pH. Adv Exp Med Biol 605:333-7 |
