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J Appl Physiol (1985). 2014 Oct 15;117(8):848-56. doi: 10.1152/japplphysiol.00439.2014. Epub 2014 Aug 21.

Strain differences in pH-sensitive K+ channel-expressing cells in chemosensory and nonchemosensory brain stem nuclei.

Author information

1
Biology Department, Carthage College, Kenosha, Wisconsin; Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
2
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
3
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin; and.
4
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin mhodges@mcw.edu.

Abstract

The ventilatory CO2 chemoreflex is inherently low in inbred Brown Norway (BN) rats compared with other strains, including inbred Dahl salt-sensitive (SS) rats. Since the brain stem expression of various pH-sensitive ion channels may be determinants of the CO2 chemoreflex, we tested the hypothesis that there would be fewer pH-sensitive K(+) channel-expressing cells in BN relative to SS rats within brain stem sites associated with respiratory chemoreception, such as the nucleus tractus solitarius (NTS), but not within the pre-Bötzinger complex region, nucleus ambiguus or the hypoglossal motor nucleus. Medullary sections (25 μm) from adult male and female BN and SS rats were stained with primary antibodies targeting TASK-1, Kv1.4, or Kir2.3 K(+) channels, and the total (Nissl-stained) and K(+) channel immunoreactive (-ir) cells counted. For both male and female rats, the numbers of K(+) channel-ir cells within the NTS were reduced in the BN compared with SS rats (P < 0.05), despite equal numbers of total NTS cells. In contrast, we found few differences in the numbers of K(+) channel-ir cells among the strains within the nucleus ambiguus, hypoglossal motor nucleus, or pre-Bötzinger complex regions in both male and female rats. However, there were no predicted functional mutations in each of the K(+) channels studied comparing genomic sequences among these strains. Thus we conclude that the relatively selective reductions in pH-sensitive K(+) channel-expressing cells in the NTS of male and female BN rats may contribute to their severely blunted ventilatory CO2 chemoreflex.

KEYWORDS:

CO2 chemoreception; K+ channels; control of breathing

PMID:
25150225
PMCID:
PMC4199991
DOI:
10.1152/japplphysiol.00439.2014
[Indexed for MEDLINE]
Free PMC Article

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