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.

ABSTRACT:

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 EC50 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.

SUBMITTER: Hsu HT 

PROVIDER: S-EPMC4288500 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature