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Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents.

Acta pharmacologica Sinica (2010-11-03)
Yi-hung CHEN, Pei-lin LIN, Hui-yu HSU, Ya-ting WU, Han-yin YANG, Dah-yuu LU, Shiang-suo HUANG, Ching-liang HSIEH, Jaung-geng LIN
RÉSUMÉ

to investigate the effects of 2'-hydroxy-4'-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. the RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥ 500 micromol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co(2+)-substituted Ca(2+)-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 micromol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K(+) current (I(KD)) and the fast-inactivating K(+) current (I(A)). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of I(A), or charybdotoxin 250 nmol/L, an inhibitor of the Ca(2+)-activated K(+) current (I(K(Ca))), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an I(KD) blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the I(KD).

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KT 5720, ≥98% (HPLC), powder