Chia Hsien Lin1, Chi Lun Wu1, Mei Shan Lin2,3, Ming Chang Liu1, Pei Lin1, Ming Cheng Tsai1
1Department of Pharmacology
2Department of Biochemistry, College of Medicine, Taipei Medical University, Taipei, Taiwan
3Institute of Pharmaceutical Science, College of Medicine, National Taiwan University, and
Tóm tắt
The effects of 2,3-butanedione monoxime (BDM) on induction of action potential bursts were studied pharmacologically on the RP4 central neuron of giant African snail (<i>Achatina fulica </i>Ferussac). The effect of okadaic acid on the neuron was also tested. The RP4 neuron showed a spontaneous firing of action potential. Okadaic acid (1 µmol/l) did not alter the frequency of spontaneous action potential while BDM (3 mmol/l) reversibly elicited bursts of potential (BoP) of the RP4 neuron. The BoP elicited by BDM (3 mmol/l) were reversed 20 min after incubation with diazoxide (500 µmol/l) while the BoP were not altered in preparations treated with okadaic acid and BDM. The BDM-elicited BoP were not inhibited after administration with (a) hexamethonium (100 µmol/l), (b) atropine (1 mmol/l), (c) <i>d</i>-tubocurarine (100 µmol/l), (d) prazosin (100 µmol/l), (e) propranolol (100 µmol/l), (f) calcium-free solution, (g) high K<sup>+</sup> (12 mmol/l) or (h) with high Mg<sup>2+</sup> (30 mmol/l) solutions. The BDM-elicited BoP were inhibited by pretreatment with KT-5720 (10 µmol/l) or H89 (10 µmol/l), the protein kinase A inhibitors. However, the BoP were not affected after application of chelerythrine (10 µmol/l) or Ro 31-8220 (10 µmol/l), the protein kinase C inhibitors. Voltage-clamped studies revealed that BDM elicited a negative slope resistance (NSR) at membrane potentials between –50 and –10 mV. The NSR was not detectable at the same membrane potential in control RP4 neuron. It is suggested that the BoP elicited by BDM were not due to (1) the synaptic effects of neurotransmitters; (2) the activation of cholinergic, adrenergic receptors, or (3) phosphatase activity of the neuron. The BDM-elicited BoP were dependent on the protein kinase A related cAMP in the neuron and the delayed outward K<sup>+</sup> current may contribute to the BDM-elicited BoP.
