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

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 [Ca2+] ([Ca2+](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 [Ca2+](i) showed that the PACAP-mediated [Ca2+](i) rise was accompanied by depolarization and action potential firing. Ni2+, a blocker of voltage-gated Ca2+ channels (VGCC) or the removal of extracellular Ca2+ reversibly inhibited the PACAP-mediated [Ca2+](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.