Differences between three inbred rat strains in number of K⁺ channel-immunoreactive neurons in the medullary raphé nucleus

Abstract

Ventilatory sensitivity to hypercapnia is greater in Dahl salt-sensitive (SS) rats than in Fawn Hooded hypertensive (FHH) and Brown Norway (BN) inbred rats. Since pH-sensitive potassium ion (K(+)) channels are postulated to contribute to the sensing and signaling of changes in CO(2)-H(+) in chemosensitive neurons, we tested the hypothesis that there are more pH-sensitive K(+) channel-immunoreactive (ir) neurons within the medullary raphé nuclei of the highly chemosensitive SS rats than in the other two strains. Medullary tissues from male and female BN, FHH, and SS rats were stained with cresyl violet or with antibodies targeting TASK-1, K(v)1.4, and Kir2.3 channels. K(+) channel-ir neurons were quantified and compared with the total neurons in the region. The total number of neurons in the medullary raphé 1) was greater in male FHH than the other male rats, 2) did not differ among the female rats, and 3) did not differ between sexes. The average number of K(+) channel-ir neurons per section was 30-60 neurons higher in the male SS than in the other rat strains. In contrast, for the females, the number of K(+) channel-ir neurons was greatest in the BN. We also found significant differences in the number of K(+) channel-ir neurons between sexes in SS (males > females) and BN (females > males) rats, but not the FHH strain. Our findings support the hypothesis for males but not for females, suggesting that both genetic background and sex are determinants of K(+) channel immunoreactivity of medullary raphé neurons, and that the expression of pH-sensitive K(+) channels in the medullary raphé does not correlate with the ventilatory sensitivity to hypercapnia.

Identifying Candidate Genes that Underlie Cellular pH Sensitivity in Serotonin Neurons Using Transcriptomics: A Potential Role for Kir5.1 Channels

“…There were also multiple non-selective cation channels, including three hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, three transient receptor potential (Trp) channels, and a purinergic receptor subunit ( P2rx5 ). Several of these differentially expressed channels have been implicated in cellular responses to pH changes in the brainstem, including Kcnk1 (TWIK-1), Kcnk3 (TASK-1), Kcnk5 (TASK-2), Kcnk9 (TASK-3), Kcna2 (Kv1.2), Kcnj4 (Kir2.3), Trpv3 (TRPV3), Kcnj10 (Kir4.1), and Kcnj16 (Kir5.1) ( Washburn et al, 2002 ; Putnam et al, 2004 ; Riley et al, 2010 ; Wang et al, 2013 ).…”

Central and peripheral chemoreceptors in sudden infant death syndrome

“…The number of potassium channel‐immunoreactive neurons in the medullary raphe also differs between males and females in some inbred rat strains (Riley et al . ).…”