Evidence for involvement of A-kinase anchoring protein in activation of rat arterial K-ATP channels by protein kinase A

Citation
Y. Hayabuchi et al., Evidence for involvement of A-kinase anchoring protein in activation of rat arterial K-ATP channels by protein kinase A, J PHYSL LON, 536(2), 2001, pp. 421-427
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
Journal title
JOURNAL OF PHYSIOLOGY-LONDON
ISSN journal
0022-3751 → ACNP
Volume
536
Issue
2
Year of publication
2001
Pages
421 - 427
Database
ISI
SICI code
0022-3751(20011015)536:2<421:EFIOAA>2.0.ZU;2-9
Abstract
1. We have investigated the possible role of A-kinase anchoring proteins (A KAPS) in protein kinase A (PKA) signalling to ATP-sensitive K+ (K-ATP) chan nels of rat isolated mesenteric arterial smooth muscle cells using whole-ce ll patch clamp and peptides that inhibit PKA-AKAP binding. 2. Intracellular Ht31 peptide (20 mum) which inhibits the PKA-AKAP interact ion, blocked K-ATP current activation by either dibutyryl cAMP or calcitoni n gene-related peptide. Ht31-proline (20 muM), which does not inhibit PKA b inding to AKAP, did not block K-ATP current activation. 3. Ht31 reduced K-ATP current activated by pinacidil and also prevented its inhibition by Rp-cAMPS, effects consistent with Ht31 blocking steady-state K-ATP channel activation by PKA. However, Ht31 did not prevent K-ATP curre nt activation by the catalytic subunit of PKA. 4. An antibody to the RII subunit of PKA showed localization of PKA near to the cell membrane. Our results provide evidence that both steady-state and receptor-driven activation of K-ATP channels by PKA involve the localizati on of PKA by an AKAP.