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Background  Naringenin (NGEN) is a citrus bioflavonoid known to have beneficial health properties; however, the ionic mechanism of its actions remains largely unclear. In this study, we attempted to evaluate the possible effects of NGEN on K +  currents in NSC-34 neuronal cells and in HEK293T cells expressing α- hSlo .    Results  NGEN increased M-type K +  current ( I  K(M) ) in a concentration-dependent manner with an EC 50  value of 9.8 μM in NSC-34 cells. NGEN shifted the activation curve of  I  K(M)  conductance to the more negative potentials. In cell-attached recordings, NGEN or flupirtine enhanced the activity of M-type K +  (K M ) channels with no changes in single-channel amplitude. NGEN (10 μM) had minimal effect on  erg -mediated K +  currents. Under cell-attached voltage-clamp recordings, NGEN decreased the frequency of spontaneous action currents and further application of linopirdine can reverse NGEN-induced inhibition of firing. In HEK293T cells expressing α- hSlo , this compound increased the amplitude of Ca 2+ -activated K +  current ( I  K(Ca) ). Under inside-out recordings, NGEN applied to the intracellular side of the detached patch enhanced the activity of large-conductance Ca 2+ -activated K +  (BK Ca ) channels. Moreover, from the study of a modeled neuron, burst firing of simulated action potentials (APs) was reduced in the presence of the increased conductances of both K M  and K Ca  channels. Fast-slow analysis of AP bursting from this model also revealed that as the conductances of both K M  and BK Ca  channels were increased by two-fold, the voltage nullcline was shifted in an upward direction accompanied by the compression of burst trajectory.    Conclusions  The present results demonstrate that activation of both K M  and BK Ca  channels caused by NGEN might combine to influence neuronal activity if similar channels were functionally co-expressed in central neurons in vivo.

bmc neuroscience

Ability of naringenin, a bioflavonoid, to activate M-type potassium current in motor neuron-like cells and to increase BKCa-channel activity in HEK293T cells transfected with α-hSlo subunit