RT Journal Article
SR Electronic
T1 Cloned muscarinic receptor subtypes expressed in A9 L cells differ in their coupling to electrical responses.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 421
OP 426
VO 34
IS 4
A1 S V Jones
A1 J L Barker
A1 N J Buckley
A1 T I Bonner
A1 R M Collins
A1 M R Brann
YR 1988
UL http://molpharm.aspetjournals.org/content/34/4/421.abstract
AB The electrophysiological responses to cholinergic stimulation of four cloned muscarinic receptor subtypes (m1-m4) were studied in A9 L cells transfected with the expression plasmids of each of the different subtypes, using the tight-seal whole-cell recording technique. Cells transfected with m1 and m3 muscarinic receptor subtypes were hyperpolarized by acetylcholine (ACh), whereas m2- and m4-transfected cells did not respond to ACh concentrations of up to 1 mM. Stimulation of both m1 and m3 muscarinic receptor subtypes evoked outward currents in cells voltage-clamped at -50 mV, associated with an increase in membrane conductance. These outward currents were blocked by atropine but not by tubocurarine. The ACh-induced currents of m1- and m3-transfected cells primarily involved potassium ions, although chloride ions also contributed to a minor extent. The potassium and chloride conductances were blocked by barium or cobalt and by buffering the intracellular calcium to low levels with 5 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid, showing a dependence of these conductances on calcium. Thus, m1- and m3-transfected cells respond to ACh in a manner that is qualitatively similar, evoking calcium-dependent potassium and chloride conductances, whereas m2- and m4-transfected cells are not coupled to electrically detectable responses in A9 L cells.