Muscarine induces two distinct current responses in adrenal chromaffin cells of the guinea-pig.
Muscarine-induced membrane responses were studied in dissociated chromaffin cells of the guinea-pig adrenal medulla, using the whole-cell version of the patch-clamp technique. Bath application of muscarine (1-10 microM) produced two distinct current responses at a holding potential of -40 mV. One is an inward current associated with an increase in current noise. This current response was sustained during stimulation and had a reversal potential of 4.5 +/- 3.4 mV (n = 6) with a negative slope conductance below about -30 mV in 12.5 mM K(+)-containing perfusate. The other is a transient outward current. This was evoked at membrane potentials more positive than -60 mV and completely suppressed by addition of 2 mM TEA to the bath solution, suggesting a possible involvement of the Ca2(+)-dependent K+ channel. Generation of the outward current response was suppressed for at least 60-90 s following 25 s muscarinic stimulation and was facilitated by activation of the nicotinic receptor. The maximum inward current seemed to be produced by 3 microM, whereas the threshold concentration required for generation of the outward current was somewhere between 3 and 10 microM. The outward current was evoked less often in cells treated with 2% collagenase for 1 h than in those treated with 0.2% for 30 min. The results suggest that guinea-pig chromaffin cells have two muscarinic receptors: one is coupled with a cation nonselective channel and the other may be related to a Ca2(+)-dependent K+ channel.
Inoue
M
M
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kuriyama
H
H
D000313:Adrenal Medulla / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009116:Muscarine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism
D002395:Catecholamines; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D009116:Muscarine; D002118:Calcium