Muscarinic inhibition of two potassium currents in guinea-pig prevertebral neurons: differentiation by extracellular cesium.
Muscarinic responses were studied in dissociated guinea-pig celiac ganglion neurons using the whole-cell voltage-clamp technique. Muscarine (0.025-1 mM; EC50 = 95 microM) administered to cells for 1.5 s evoked inward shifts in holding current in 53 of 74 cells. The amplitude of the inward current transients decreased with hyperpolarization and the null potential averaged -71 +/- 3.4 mV (n = 11). The currents that underlie the responses to muscarine were examined with hyperpolarizing voltage stepping protocols to -100 mV from a holding potential of -30 mV. Eighty-one per cent of cells displayed voltage-dependent current relaxations characteristic of the M-potassium current. Twenty per cent of responding cells displayed no M-current but only a voltage-independent current consistent with a leak current. In the latter type of cells, the muscarine-evoked inward currents reversed near EK and became outward at more hyperpolarized potentials. Analysis of steady state I-V relationships before and after bath application of muscarine showed that the two muscarine-sensitive potassium currents were distributed differently among three types of cells: (i) with M-current (18%); (ii) with leak current (18%); and (iii) with M-current and with leak current (64%). Cesium and barium were used to differentiate the M-current and the muscarine-sensitive leak current. Barium (2 mM) reduced the M-current and the leak potassium current, whereas cesium (2 mM) reduced the M-current but did not affect leak current. Thus, barium reduced the amplitude of muscarinic responses by 79% but cesium reduced them by only 14%. We conclude that muscarinic responses in guinea-pig celiac neurons are produced by suppression of two K+ currents: the M-current and a muscarine-sensitive leak current. These two currents are differentially susceptible to the potassium channel blockers barium and cesium.
Coggan
J S
JS
Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724.
Purnyn
S L
SL
Knoper
S R
SR
Kreulen
D L
DL
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000502:physiology*; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009116:Muscarine / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*
D015221:Potassium Channels; D002586:Cesium; D001464:Barium; D009116:Muscarine; D000109:Acetylcholine