Coupling of m2 and m4 muscarinic acetylcholine receptor subtypes to Ca2+-dependent K+ channels in transformed NL308 neuroblastoma x fibroblast hybrid cells

Mami Noda, M. Katayama, D. A. Brown, J. Robbins, S. J. Marsh, N. Ishizaka, K. Fukuda, N. Hoshi, S. Yokoyama, H. Higashida

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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 Ca2+-dependent K+ current. However, the outward current produced in m2- and m4-transformed cells was blocked by pretreatment with 5 ng ml-3 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 I(K(Ca)) whereas m1 and m3 receptors activate a similar process through a different, PTX-insensitive G-protein.

Original languageEnglish
Pages (from-to)215-224
Number of pages10
JournalProceedings of the Royal Society B: Biological Sciences
Issue number1332
Publication statusPublished - Jan 1 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Environmental Science(all)
  • Agricultural and Biological Sciences(all)

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