title: Mechanisms and roles of muscarinic activation in guinea-pig adrenal medullary cells.
abstract: Muscarinic receptors are expressed in the adrenal medullary (AM) cells of various mammals, but their physiological roles are controversial. Therefore, the ionic mechanism for muscarinic receptor-mediated depolarization and the role of muscarinic receptors in neuronal transmission were investigated in dissociated guinea-pig AM cells and in the perfused guinea-pig adrenal gland. Bath application of muscarine induced an inward current at -60 mV. This inward current was partially suppressed by quinine with an IC(50) of 6.1 μM. The quinine-insensitive component of muscarine-induced currents changed the polarity at -78 mV and was inhibited by bupivacaine, a TWIK-related acid-sensitive K(+) (TASK) channel inhibitor. Conversely, the current-voltage relationship for the bupivacaine-insensitive component of muscarine currents showed a reversal potential of -5 mV and a negative slope below -40 mV. External application of La(3+) had a double action on muscarine currents of both enhancement and suppression. Immunoblotting and immunocytochemistry revealed expression of TASK1 channels and cononical transient receptor potential channels 1, 4, 5, and 7 in guinea-pig AM cells. Retrograde application of atropine reversibly suppressed transsynaptically evoked catecholamine secretion from the adrenal gland. The results indicate that muscarinic receptor stimulation in guinea-pig AM cells induces depolarization through inhibition of TASK channels and activation of nonselective cation channels and that muscarinic receptors are involved in neuronal transmission from the splanchnic nerve.
authors: Dept. of Cell and Systems Physiology, Univ. of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan. minoue@med.uoeh-u.ac.jp
authors: Masumi
authors: M
authors: Inoue
authors: Keita
authors: K
authors: Harada
authors: Hidetada
authors: H
authors: Matsuoka
authors: Jun
authors: J
authors: Nakamura
authors: Akira
authors: A
authors: Warashina
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain / Q000502:physiology; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D011976:Receptors, Muscarinic; C420132:potassium channel subfamily K member 3; D009116:Muscarine