Coupling of m2 and m4 muscarinic acetylcholine receptor subtypes to Ca(2+)-dependent K+ channels in transformed NL308 neuroblastoma x fibroblast hybrid cells.
Proc Biol Sci
; 251(1332): 215-24, 1993 Mar 22.
Article
em En
| MEDLINE
| ID: mdl-8097328
ABSTRACT
Muscarinic acetylcholine receptor (mAChR) subtype (m1-m4)-specific cDNAs were transfected into NL308 neuroblastoma-fibroblast hybrid cells and clones expressing each of the individual mAChR subtypes m1, m2, m3 and m4 obtained. Acetylcholine increased phosphoinositide (PI) turnover in m1- and m3-transformed cells, but did not produce detectable changes in m2- and m4-transformed cells. In cells expressing m1 and m3 subtypes, ACh produced an initial outward K+ current, followed by a cationic current. In cells expressing m2 and m4 receptors, only the initial K+ current was detected. The outward currents were associated with a rise in intracellular Ca2+ as measured with Fura-2 or Indo-1, and were inhibited by chelating intracellular Ca2+ with external BAPTA-AM, or by external charybdotoxin or Ba2+ hence they were attributed to the activation of a Ca(2+)-dependent K+ current. However, the outward current produced in m2- and m4-transformed cells was blocked by pretreatment with 5 ng ml-1 Pertussis toxin (PTX), whereas that in m1- and m3-transformed cells was not. These results suggest that m2- and m4-receptors in transformed NL308 cells coupled to PTX-sensitive G-protein which is capable of mobilizing intracellular Ca2+ and activate IK(Ca), whereas m1 and m3 receptors activate a similar process through a different, PTX-insensitive G-protein.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Potássio
/
Cálcio
/
Receptores Muscarínicos
Limite:
Animals
Idioma:
En
Ano de publicação:
1993
Tipo de documento:
Article