Pre- and post-synaptic muscarinic receptors in thin slices of rat adrenal gland.
The effects of activation of muscarinic receptors on chromaffin cells and splanchnic nerve terminals were studied in a rat adrenal slice preparation. In chromaffin cells, muscarine induced a transient hyperpolarization followed by a depolarization associated with cell spiking. The hyperpolarization was blocked by charybdotoxin (1 microM) and tetraethylammonium chloride (TEA, 1 mM), but was not affected by 200 microM Cd2+ or removal of external Ca2+, consistent with activation of BK channels. This would follow internal Ca2+ mobilization, as shown by Ca2+ imaging with fura-2 on isolated chromaffin cells in culture. Under voltage-clamp, outward BK currents were insensitive to MT3 toxin, a specific muscarinic m4 receptor antagonist. In contrast, muscarine-induced depolarization was due to a m4 receptor-mediated inward current blocked by MT3 toxin. This current was permeable to cations and was associated with Ca2+ entry and subsequently, Ca2+-induced Ca2+ release. Finally, both muscarine (25 microM) and oxotremorine (10 microM) decreased the amplitude and frequency of KCI-evoked excitatory postsynaptic currents, without affecting quantal size, consistent with a presynaptic inhibitory effect. Taken together, our data suggest that activation of m4 and probably m3 muscarinic receptors results in a strong, long-lasting excitation of chromaffin cells, as well as an uncoupling of synaptic inputs onto these cells.
Barbara
J G
JG
Laboratoire de Pharmacologie et Physiopathologie, Cellulaires, CNRS URA600, Université Louis Pasteur de Strasbourg, Illkirch, France. jean-gael_barbara@nymc.edu
Lemos
V S
VS
Takeda
K
K
D000109:Acetylcholine / Q000378:metabolism; D000311:Adrenal Glands / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D002118:Calcium / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology*; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D043587:Receptor, Muscarinic M3; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D017661:Receptors, Presynaptic; D000109:Acetylcholine; D002118:Calcium