Differential expression of large-conductance ca 2+-activated K channels in the carotid body between DBA/2J and A/J strains of mice

Toshiki Otsubo, Eric W. Kostuk, Alexander Balbir, Koichi Fujii, Machiko Shirahata

Research output: Contribution to journalArticle

Abstract

The carotid body (CB) is a primary chemosensory organ for arterial hypoxia. Inhibition of K channels in chemosensory glomus cells (GCs) are considered to be responsible for hypoxic chemoreception and/or chemotransduction of the CB. Hypoxic sensitivity of large-conductance calcium-activated K (BK) channels has been established in the rat CB. Our previous work has shown the BK channel β2 subunits are more expressed in the CB of the DBA/2J mouse than that of the A/J mouse. Because the DBA/2J mouse is more sensitive to hypoxia than the A/J mouse, our general hypothesis is that BK channels play a role in the sensitivity of the mouse CB to mild hypoxia. We performed vigorous analysis of the gene expression of α, β2, and β4 subunits of BK channels in the CB. We found that α and β2 subunits were expressed more in the CB of the DBA/2J mice than that of the A/J mice. No differences were found in the β4 subunit expression.These differences were not seen in the neighboring tissues, the superior cervical ganglion and the carotid artery, suggesting that the differences are CB specific. Further, the sensitivity of BK channels in GCs to mild hypoxia was examined in patch clamp experiments using undissociated CBs. Iberiotoxin significantly inhibited K current of GCs in the DBA/2J mice, but not in the A/J mice. When reducing PO 2 to ~70mmHg, K current reversibly decreased in GCs of the DBA/2J, but not of the A/J mice. In the presence of iberiotoxin, mild hypoxia did not inhibit K current in either strains. Thus, the data suggest that BK channels in GCs of the DBA/2J mice are sensitive to mild hypoxia. Differential expression of BK channel β subunits in the CBs may, at least in part, explain the different hypoxic sensitivity in these mouse strains.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalFrontiers in Cellular Neuroscience
Issue numberOCTOBER
DOIs
StatePublished - Oct 11 2011

Fingerprint

Carotid Body
Large-Conductance Calcium-Activated Potassium Channels
Inbred DBA Mouse
Calcium-Activated Potassium Channels
Superior Cervical Ganglion
Carotid Arteries
Hypoxia
Gene Expression

Keywords

  • Chemoreceptor
  • Glomus cell
  • Hypoxia
  • Oxygen
  • Patch clamp
  • RT-PCR

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Differential expression of large-conductance ca 2+-activated K channels in the carotid body between DBA/2J and A/J strains of mice. / Otsubo, Toshiki; Kostuk, Eric W.; Balbir, Alexander; Fujii, Koichi; Shirahata, Machiko.

In: Frontiers in Cellular Neuroscience, No. OCTOBER, 11.10.2011, p. 1-8.

Research output: Contribution to journalArticle

Otsubo, Toshiki ; Kostuk, Eric W. ; Balbir, Alexander ; Fujii, Koichi ; Shirahata, Machiko. / Differential expression of large-conductance ca 2+-activated K channels in the carotid body between DBA/2J and A/J strains of mice. In: Frontiers in Cellular Neuroscience. 2011 ; No. OCTOBER. pp. 1-8.
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abstract = "The carotid body (CB) is a primary chemosensory organ for arterial hypoxia. Inhibition of K channels in chemosensory glomus cells (GCs) are considered to be responsible for hypoxic chemoreception and/or chemotransduction of the CB. Hypoxic sensitivity of large-conductance calcium-activated K (BK) channels has been established in the rat CB. Our previous work has shown the BK channel β2 subunits are more expressed in the CB of the DBA/2J mouse than that of the A/J mouse. Because the DBA/2J mouse is more sensitive to hypoxia than the A/J mouse, our general hypothesis is that BK channels play a role in the sensitivity of the mouse CB to mild hypoxia. We performed vigorous analysis of the gene expression of α, β2, and β4 subunits of BK channels in the CB. We found that α and β2 subunits were expressed more in the CB of the DBA/2J mice than that of the A/J mice. No differences were found in the β4 subunit expression.These differences were not seen in the neighboring tissues, the superior cervical ganglion and the carotid artery, suggesting that the differences are CB specific. Further, the sensitivity of BK channels in GCs to mild hypoxia was examined in patch clamp experiments using undissociated CBs. Iberiotoxin significantly inhibited K current of GCs in the DBA/2J mice, but not in the A/J mice. When reducing PO 2 to ~70mmHg, K current reversibly decreased in GCs of the DBA/2J, but not of the A/J mice. In the presence of iberiotoxin, mild hypoxia did not inhibit K current in either strains. Thus, the data suggest that BK channels in GCs of the DBA/2J mice are sensitive to mild hypoxia. Differential expression of BK channel β subunits in the CBs may, at least in part, explain the different hypoxic sensitivity in these mouse strains.",
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AU - Kostuk, Eric W.

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AU - Fujii, Koichi

AU - Shirahata, Machiko

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AB - The carotid body (CB) is a primary chemosensory organ for arterial hypoxia. Inhibition of K channels in chemosensory glomus cells (GCs) are considered to be responsible for hypoxic chemoreception and/or chemotransduction of the CB. Hypoxic sensitivity of large-conductance calcium-activated K (BK) channels has been established in the rat CB. Our previous work has shown the BK channel β2 subunits are more expressed in the CB of the DBA/2J mouse than that of the A/J mouse. Because the DBA/2J mouse is more sensitive to hypoxia than the A/J mouse, our general hypothesis is that BK channels play a role in the sensitivity of the mouse CB to mild hypoxia. We performed vigorous analysis of the gene expression of α, β2, and β4 subunits of BK channels in the CB. We found that α and β2 subunits were expressed more in the CB of the DBA/2J mice than that of the A/J mice. No differences were found in the β4 subunit expression.These differences were not seen in the neighboring tissues, the superior cervical ganglion and the carotid artery, suggesting that the differences are CB specific. Further, the sensitivity of BK channels in GCs to mild hypoxia was examined in patch clamp experiments using undissociated CBs. Iberiotoxin significantly inhibited K current of GCs in the DBA/2J mice, but not in the A/J mice. When reducing PO 2 to ~70mmHg, K current reversibly decreased in GCs of the DBA/2J, but not of the A/J mice. In the presence of iberiotoxin, mild hypoxia did not inhibit K current in either strains. Thus, the data suggest that BK channels in GCs of the DBA/2J mice are sensitive to mild hypoxia. Differential expression of BK channel β subunits in the CBs may, at least in part, explain the different hypoxic sensitivity in these mouse strains.

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