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 ?-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 ?-hSlo. RESULTS: NGEN increased M-type K(+) current (I(K(M))) in a concentration-dependent manner with an EC50 value of 9.8 ?M 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 ?M) 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 ?-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

REPOSITORIES: biostudies-literature