Interaction between P2 antagonists and Ca²⁺-dependent K⁺ channel antagonists in the contraction of the guinea-pig vas deferens

Abstract

Contractions evoked by electrical stimulation of 50 pulses with 40 Hz to the guinea-pig vas deferens consist of L- and T-type Ca²⁺ channel-mediated adrenergic (α₁) component and L-type Ca²⁺ channel-mediated purinergic component. SK and BK channels closely located L- and T-type Ca²⁺ channels greatly affect on the contraction, especially α₁ adrenergic component. The α₁ component consisting of the early and late components was obtained by the treatment of P2 antagonist. P2 antagonist suramin (300 μM) not only antagonizes P2x purinoceptors but also activates SK channels via P2Y2 purinoceptors (Ming et al). PPADS (30 μM)-treated vas deferens revealed large early α₁ component suggesting that PPADS itself might inactivate SK channels. α,β-Methylene ATP (desensitization of P2x purinoceptors, 10 μM) did not affect directly K⁺ channels. SK channel antagonist apamin (100 nM) amplified both early- and late-α₁ components. BK channel antagonist iberiotoxin (100 nM) amplified the late-α₁ component without affecting on the early-α₁ component. On the contrary, another BK channel antagonist CTX (100 nM) amplified not only the late-α₁ component but also the early-α₁ component. CTX seemed to deprive the action of PPADS to antagonize P2x purinoceptors. The results suggest that α,β-methylene ATP was suitable for antagonizing P2x purinoceptors, and that apamin and iberiotoxin were more suitable for antagonizing SK and BK channels, respectively. [J Physiol Sci. 2006;56 Suppl:S144]