Li Yen Mae Huang

Peptides: Pharmacological evidence for three forms of chemical excitability in cultured mouse spinal neurons

Intracellular recordings from mouse spinal neurons growing in monolayer culture were used to study the effects of opioid peptides and substance P on neuronal excitability. Three actions were observed: 1) transmitter-like actions, including a presumptive increase in Cl− conductance and a rapidly desensitizing excitation; 2) modulation of amino acid responses in the absence of, or independent of any other membrane effects; and 3) alteration in spike threshold in the absence of, or independent of any other membrane effects. All three types of effect were observed on the same cell. The same general classes of chemical excitability have been observed with a variety of non-peptide substances, indicating that the multiple effects of peptides are superficially not unique.

Interaction between batrachotoxin and yohimbine.

The neurotoxins, batrachotoxin and veratridine, are specific activators of sodium channels and cause an increase in the rate of 22Na uptake in neuroblastoma cells. Yohimbine, an indolakylamine alkaloid, inhibits this batrachotoxin-induced 22Na uptake. The dose-response curve of yohimbine suggest that the inhibitor acts reversibly on a single class of binding sites with dissociation constant of 3--4 x 10(-5) M. The dissociation constant is not affected by depolarization from--41 to 0 mV. Kinetic and equilibrium experiments indicate that yohimbine is a competitive inhibitor of the action of batrachotoxin. These results support the conclusion that yohimbine inhibitis the sodium flux by acting on the channel gating mechanism rather than by occluding the channels.