An M2-like muscarinic receptor enhances a delayed rectifier K+ current in rat sympathetic neurones.
OBJECTIVE
Resting superior cervical ganglion (SCG) neurones are phasic cells that switch to a tonic mode of firing upon muscarinic receptor stimulation. This effect is partially due to the muscarinic inhibition of the M-current. Because delayed rectifier K+ channels are essential to sustain tonic firing in central neurones, we asked whether the delayed rectifier current IKV in SCG neurones was modulated by the muscarinic receptors expressed in these cells.


METHODS
Whole-cell patch-clamp records of M-current and IKV were done in cultured or acutely dissociated rat SCG neurones. To characterize the receptor that regulates IKV, cells were bathed with muscarinic agonists and antagonists, relatively specific for receptor subtypes.


RESULTS
The muscarinic agonist oxotremorine-M (Oxo-M) enhanced IKV by approximately 46% relative to its basal value. This effect remained unaltered when M-current was suppressed by linopirdine or Ba2+. Enhancement of IKV was insensitive to the M1-antagonist pirenzepine, whereas it was inhibited (approximately 60%) by the M2/4-antagonist himbacine. Further, the relatively specific M2-agonist bethanechol was as potent as Oxo-M in enhancing IKV. The modulation of IKV was insensitive to pertussis toxin (PTX), but was severely attenuated when internal ATP was replaced by its non-hydrolysable analogue AMP-PNP.


CONCLUSIONS
These results suggest that an M2-like muscarinic receptor couples to a PTX-insensitive G-protein and to an ATP-dependent pathway to enhance IKV. Modulation of IKV must be taken into consideration in order to understand more precisely how muscarinic receptors acting on different ion channels regulate sympathetic excitability.
Cruzblanca
H
H
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col. 28045, México. cruzblan@cgic.ucol.mx
D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D005663:Furans / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000187:drug effects / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000470:Alkaloids; D051668:Delayed Rectifier Potassium Channels; D005663:Furans; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D009281:Naphthalenes; D010880:Piperidines; D043585:Receptor, Muscarinic M2; D018723:Bethanechol; D010095:Oxotremorine; C042743:oxotremorine M; D000255:Adenosine Triphosphate; C048172:himbacine