Electrophysiological effects of piperazine and diethylcarbamazine on Ascaris suum somatic muscle.
1 Electrophysiological recordings were made from the bag region of Ascaris suum muscle. Membrane potential and input conductance or membrane current under voltage clamp were measured. 2 In high-Cl- Ringer, bath-applied piperazine, at concentrations greater than 10(-4)M, produced a dose-dependent and reversible increase in input conductance associated with a hyperpolarizing potential. The increase in input conductance was reduced when the preparations were bathed in low-Cl- Ringer. Gamma-Aminobutyric acid (GABA) and piperazine reversal potentials were measured with a voltage clamp on the same cells using iontophoretic application of the agonists. The reversal potentials were the same and close to the predicted Nernst Cl- potential (-65 mV). When GABA and piperazine were applied simultaneously piperazine reversibly reduced the amplitude of the control outward GABA current response. It was concluded that piperazine acts as a GABA agonist of low potency on the extra-synaptic GABA receptors of the bag, mediating an increase in Cl- conductance. 3 Acetylcholine was applied iontophoretically within 100 micron of the bag region while the preparation was bathed in a low-Ca2+, low-Cl- Ringer. The response under voltage clamp was a dose-dependent inward current associated with an increase in input conductance. This response was reversibly antagonized by 3 X 10(-5)M tubocurarine, high concentrations of diethylcarbamazine (10(-3) to 10(-2)M) but not high concentrations of piperazine (10(-3) to 10(-2)M). It was concluded that there are extra-synaptic acetylcholine receptors on the bag region of Ascaris muscle and that diethylcarbamazine but not piperazine acts as an antagonist. 4 Bath-applied diethylcarbamazine (10(-4) to 2 X 10(-3)M) produced a reversible dose-dependent depolarization of the membrane potential which was associated with an increase in the amplitude and frequency of spontaneous depolarizing potentials in active preparations at 32 degrees C to 35 degrees C in high-Cl- Ringer. The excitatory action of diethylcarbamazine was not blocked by 3 X 10(-5)M tubocurarine. Diethylcarbamazine (10(-4) to 10(-3)M) had no effect on the outward current response to GABA iontophoresis. Diethylcarbamazine (10(-4) to 10(-2)M) reversibly antagonized in a dose-dependent manner the delayed rectification of the bag membrane. In a low-Ca2+, low-Cl- Ringer, diethylcarbamazine (10(-4) to 2 X 10(-3)M) reversibly antagonized the voltage-sensitive outward current of the bag. This effect was mimicked by high-K+ Ringer or perfusion with 4-aminopyridine (10(-3) to 2 X 10(-3)M). It was concluded that diethylcarbamazine did not react with the GABA receptor but antagonized a voltage-sensitive K+ conductance.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D001200:Ascaris / Q000187:drug effects*; D004049:Diethylcarbamazine / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D007478:Iontophoresis; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000969:Antinematodal Agents; D010879:Piperazines; D005680:gamma-Aminobutyric Acid; C006589:piperazine citrate; D000109:Acetylcholine; D004049:Diethylcarbamazine