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Pituitary adenylate cyclase‐activating polypeptide (PACAP) stimulates the oxygen sensing type I (glomus) cells of rat carotid bodies via reduction of a background TASK‐like K + current
Author(s) -
Xu Fenglian,
Tse Frederick W.,
Tse Amy
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04468.x
Subject(s) - pituitary adenylate cyclase activating peptide , depolarization , endocrinology , medicine , vasoactive intestinal peptide , receptor , carotid body , adenylate kinase , tetraethylammonium , channel blocker , chemistry , protein kinase a , neuropeptide , biology , biochemistry , kinase , calcium , potassium , organic chemistry , stimulation
Pituitary adenylate cyclase‐activating polypeptide (PACAP)‐deficient mice are prone to sudden neonatal death and have reduced respiratory response to hypoxia. Here we found that PACAP‐38 elevated cytosolic [Ca 2+ ] ([Ca 2+ ] i ) in the oxygen sensing type I cells but not the glial‐like type II (sustentacular) cells of the rat carotid body. This action of PACAP could not be mimicked by vasoactive intestinal peptide but was abolished by PACAP 6‐38, implicating the involvement of PAC 1 receptors. H89, a protein kinase A (PKA) inhibitor attenuated the PACAP response. Simultaneous measurement of membrane potential and [Ca 2+ ] i showed that the PACAP‐mediated [Ca 2+ ] i rise was accompanied by depolarization and action potential firing. Ni 2+ , a blocker of voltage‐gated Ca 2+ channels (VGCC) or the removal of extracellular Ca 2+ reversibly inhibited the PACAP‐mediated [Ca 2+ ] i rise. In the presence of tetraethylammonium (TEA) and 4‐aminopyridine (4‐AP), PACAP reduced a background K + current. Anandamide, a blocker of TWIK‐related acid‐sensitive K + (TASK)‐like K + channel, occluded the inhibitory action of PACAP on K + current. We conclude that PACAP, acting via the PAC 1 receptors coupled PKA pathway inhibits a TASK‐like K + current and causes depolarization and VGCC activation. This stimulatory action of PACAP in carotid type I cells can partly account for the role of PACAP in respiratory disorders.