Nitric oxide activates ATP-dependent K channels in human eosinophils

Abstract: Nitric oxide (NO) affects the function of ion channels in many cell types, but its role in the regulation of eosinophil ion channels is unknown. In this study, we used the perforated patch-clamp method to investigate the effect of endogenous and exogenous NO on eosinophil ion channels. Using the NO synthase inhibitor, N-nitro-L-arginine methyl es-ter, we showed that endogenous NO did not affect the whole-cell current in eosinophil. However, two NO donors, S-nitroso-glutathione and S-nitroso-N-acetyl penicillamine, activated whole-cell currents via a NO/cGMP-dependent pathway. Ion substitution and pharmacological studies showed that NO-acti-vated currents were carried by K ions, likely through ATP-dependent K channels (KATP). Al-though RT-PCR studies showed the expression of several classes of K channels in human eosino-phils, NO donors affected only KATP channel func-tion. We conclude that NO, at concentrations likely to be encountered in vivo, could prevent eosinophil activation by opening KATP channels. J