Sulfonylurea-sensitive K+ channels and their probable role for the membrane potential of mouse motor nerve endings.
We studied the effect of the KATP channel blockers tolbutamide and glibenclamide on presynaptic membrane currents in the mouse M. triangularis sterni preparation using the perineural recording technique. Both sulfonylureas blocked part of the fast K+ component within 2 min after application. The block was much more pronounced under glucose-free conditions and was completely reversible by washing. Addition of glucose to glucose-free bath solution also reduced the K+ component. A further effect of the sulfonylureas was observed under glucose-free conditions. With a delay of 5 to 10 min, the nodal Na+ component began to diminish and disappeared within 30 min. This was associated with a dramatic increase in spontaneous quantal transmitter release suggesting that the block of sulfonylurea-sensitive K+ channels causes depolarization of motor nerve terminals and fibres thus inactivating Na+ channels. Tetraethylammonium (TEA) which blocks ATP-dependent K+ channels in high concentrations caused, under glucose-free conditions, the same delayed effect as the sulfonylureas. This delayed effect was fully reversible by washing with glucose-containing, but not with glucose-free solution. Our findings strongly suggest that KATP channels exist in mammalian motor nerve endings and that under hypoglycemic conditions these channels open and become essential for the maintenance of the membrane potential.
Deist
M
M
Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität Giessen, Federal Republic of Germany.
Repp
H
H
Dreyer
F
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004594:Electrophysiology; D005947:Glucose / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008839:Microelectrodes; D009045:Motor Endplate / Q000187:drug effects*; D009046:Motor Neurons / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D000255:Adenosine Triphosphate; D005947:Glucose