Pituitary adenylate cyclase-activating polypeptide activates KATPcurrent in rat atrial myocytes

Autor: Alex J. Baertschi, Anne Baron, Angela Roatti, Dominique Monnier
Přispěvatelé: Centre médical universitaire de Genève (CMU)
Rok vydání: 2001
Předmět:
medicine.medical_specialty
Patch-Clamp Techniques
Potassium Channels
Physiology
Muscle Fibers
Skeletal
Vasoactive intestinal peptide
Gene Expression
Neuropeptide
Adenylate kinase
Biology
Cyclase
03 medical and health sciences
Adenosine Triphosphate
0302 clinical medicine
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Physiology (medical)
Internal medicine
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Cyclic AMP
medicine
Animals
Heart Atria
RNA
Messenger
Patch clamp
Enzyme Inhibitors
ComputingMilieux_MISCELLANEOUS
Cells
Cultured
Protein Kinase C
Protein kinase C
030304 developmental biology
Sulfonamides
0303 health sciences
Reverse Transcriptase Polymerase Chain Reaction
Myocardium
Neuropeptides
Isoquinolines
Cyclic AMP-Dependent Protein Kinases
Rats
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
Pituitary adenylate cyclase-activating peptide
Endocrinology
Pituitary Adenylate Cyclase-Activating Polypeptide
Signal transduction
Cardiology and Cardiovascular Medicine
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Signal Transduction
Vasoactive Intestinal Peptide
Zdroj: AJP-Heart and Circulatory Physiology
AJP-Heart and Circulatory Physiology, American Physiological Society, 2001, 280 (3), pp.H1058-H1065. ⟨10.1152/ajpheart.2001.280.3.H1058⟩
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.2001.280.3.h1058
Popis: Because the electrophysiological effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on the heart are little known, we studied the regulation of the atrial ATP-sensitive K+(KATP) current by PACAP on primary cultured neonatal rat atrial myocytes. PACAP-38 stimulates cAMP production with EC50= 0.28 nmol/l ( r = 0.92, P < 0.02). PACAP-38 and PACAP-27 (10 nmol/l) have similar maximal effects, whereas 100 nmol/l vasoactive intestinal polypeptide (VIP) is 2.7 times less effective ( P < 0.05). RT-PCR shows the presence of cloned PACAP receptors PAC1(≥2 isoforms), VPAC1, and VPAC2. PACAP-38 dose dependently activates the whole cell atrial KATPcurrent with EC50= 1–3 nmol/l ( n = 44). Maximal effects occur at 10 nmol/l (91 ± 15 pA/pF, n = 18). Diazoxide further increases the PACAP-activated current by 78% ( P < 0.05; n = 6). H89(500 nmol/l), a protein kinase A (PKA) inhibitor, reduces the PACAP-activated KATPcurrent to 17.8 ± 9.6% ( n = 5) of the maximal diazoxide-induced current and totally inhibits the cAMP-induced KATPcurrent. A protein kinase C (PKC) inhibitor peptide (50 μmol/l) in the pipette reduces the PACAP-38-induced KATPcurrent to 33 ± 17 pA/pF ( P < 0.05, n = 6) without significantly affecting the currents induced by cAMP or VIP. The results suggest that: 1) PAC1, VPAC1, and VPAC2are present in atrial myocytes; and 2) PACAP-38 activates the atrial KATPchannels through both PKA and PKC pathways.
Databáze: OpenAIRE
Externí odkaz: