Pituitary adenylate cyclase-activating polypeptide activates K-ATP currentin rat atrial myocytes

Citation
A. Baron et al., Pituitary adenylate cyclase-activating polypeptide activates K-ATP currentin rat atrial myocytes, AM J P-HEAR, 280(3), 2001, pp. H1058-H1065
Citations number
39
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
ISSN journal
03636135 → ACNP
Volume
280
Issue
3
Year of publication
2001
Pages
H1058 - H1065
Database
ISI
SICI code
0363-6135(200103)280:3<H1058:PACPAK>2.0.ZU;2-I
Abstract
Because the electrophysiological effects of pituitary adenylate cyclase-act ivating polypeptide (PACAP) on the heart are little known, we studied the r egulation of the atrial ATP-sensitive K+ (K-ATP) current by PACAP on primar y cultured neonatal rat atrial myocytes. PACAP-38 stimulates cAMP productio n with EC50 = 0.28 nmol/l (r = 0.92, P < 0.02). PACAP-38 and PACAP-27 (10 n mol/l) have similar maximal effects, whereas 100 nmol/l vasoactive intestin al polypeptide (VIP) is 2.7 times less effective (P < 0.05). RT-PCR shows t he presence of cloned PACAP receptors PAC(1) (greater than or equal to2 iso forms), VPAC(1), and VPAC(2). PACAP-38 dose dependently activates the whole cell atrial KATP current with EC50 = 1-3 nmol/l (n = 44). Maximal effects occur at 10 nmol/l (91 +/- 15 pA/pF, n = 18). Diazoxide further increases t he PACAP-activated current by 78% (P < 0.05; n = 6). H-89 (500 nmol/l), a p rotein kinase A (PKA) inhibitor, reduces the PACAP-activated K-ATP current to 17.8 +/- 9.6% (n = 5) of the maximal diazoxide-induced current and total ly inhibits the cAMP-induced K-ATP current. A protein kinase C (PKC) inhibi tor peptide (50 <mu>mol/l) in the pipette reduces the PACAP-38-induced K-AT P current to 33 +/- 17 pA/pF (P < 0.05, n = 6) without significantly affect ing the currents induced by cAMP or VIP. The results suggest that: 1) PAC1, VPAC1, and VPAC2 are present in atrial myocytes; and 2) PACAP-38 activates the atrial KATP channels through both PKA and PKC pathways.