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

• Published in: Journal of applied physiology (1985) Vol. 117; no. 8; pp. 848 - 856
• Main Authors: Martino, Paul F, Olesiak, S, Batuuka, D, Riley, D, Neumueller, S, Forster, H V, Hodges, M R
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 15.10.2014
• Subjects: Animals; Brain; Brain Stem - metabolism; Brain Stem - physiology; Carbon Dioxide - metabolism; Chemoreceptor Cells - metabolism; Chemosensory perception; Female; Gene expression; Genomics; Immunology; Male; Neuropsychology; Potassium Channels - metabolism; Rats; Rats, Inbred BN; Rats, Inbred Dahl; Rodents; K+ channels; CO2 chemoreception; control of breathing
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00439.2014

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.