Tubocurarine suppresses slow calcium-dependent after-hyperpolarization in guinea-pig inferior mesenteric ganglion cells.
Intracellular recordings were made from neurones of the isolated guinea-pig inferior mesenteric ganglia. Single-spike potentials evoked by either depolarizing current pulses applied through the recording micro-electrode or stimulation of the hypogastric nerves were followed by an after-hyperpolarization (a.h.). The spike a.h. in 40% of the neurones, referred to herein as type I, had a relatively short duration (less than 50 ms) and exhibited a monophasic decay with a mean time constant (tau) of 11.4 ms. In the remaining cells (type II), the spike was followed by a long a.h. (greater than 100 ms) having a double-exponential decay; the fast and slow components of the a.h. are termed a.h.f and a.h.s, respectively, and they had mean tau values of 11.4 and 74 ms, respectively. A.h.f and a.h.s of type II neurones were reduced by membrane hyperpolarization and reversed their polarities between -80 and -90 mV. The reversal potentials shifted in a manner closely predicted by the Nernst equation as external K+ concentration was increased. Superfusion of low-Ca2+ high-Mg2+ solution to type II neurones reduced the a.h.f and a.h.s by 32 and 82%, respectively, indicating that a.h.s is largely Ca2+-dependent. Application of (+)-tubocurarine (10-100 microM) reversibly suppressed the a.h.s without affecting a.h.f in a concentration-dependent manner. Following a short train of action potentials evoked from type II neurones, the post-tetanic hyperpolarization (p.t.h.) was similarly depressed by (+)-tubocurarine in a dose-dependent manner. (+)-tubocurarine did not significantly change the amplitude of Ca2+-dependent spike potentials evoked in neurones bathed in Na+-free high-Ca2+ plus tetraethylammonium (5-10 mM) solution. The results indicate that (+)-tubocurarine selectively suppresses a.h.s, a slow Ca2+-dependent a.h., the consequence of which is a facilitation of repetitive discharges of the cells.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003864:Depression, Chemical; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D013569:Synapses / Q000502:physiology; D013997:Time Factors; D014403:Tubocurarine / Q000494:pharmacology*
D011188:Potassium; D002118:Calcium; D014403:Tubocurarine