Effects Of Hesperitin On Human Kv1.5 Channels,Nav1.5 Channels And On I_kur And I_Na In Human Atrial Myocytes

Part?Effects of hesperetin on Kv1.5 channels expressed in HEK 293 cellsObjective:The current study aimed at investigating the inhibitory effects of hesperetin?HSP?on human cardiac Kv1.5 channels which were stably expressed in human embryonic kidney 293?HEK293?cells.Methods:The effects of hesperetin on human cardiac Kv1.5 channels expressed in HEK 293 cells were examined using whole-cell patch-clamp techniques.Results:Hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition(IC₅₀)of 23.15??with a Hill coefficient of 0.89.The current was maximally diminished about 71.36%at a concentration of 300?M hesperetin.Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5,while negative shifted the steady-state inactivation curve.Hesperetinalso accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents.Block of Kv1.5 currents by hesperetin was in a frequency dependent manner.However,inclusion of 30?M hesperetin in pipette solution produced no effect on Kv1.5 channel current,while the current were remarkable and reversibly inhibited by extracellular application of 30?M hesperetin.Conclusion:Hesperetin is a potent inhibitor of Kv1.5 channel,with blockade probably due to blocking of both open state and inactivated state channels from outside of the cellPart?Effects of hesperetin on Nav1.5 channels expressed in HEK 293 cellsAim:The current study aimed at investigating the inhibitory effects of hesperetin?HSP?on human cardiac Nav1.5 channels which were stably expressed in human embryonic kidney 293?HEK293?cells.Methods:The effects of hesperetin on human cardiac Nav1.5 channels expressed in HEK 293 cells were examined using whole-cell patch-clamp techniques.Result:Nav1.5 currents were potently and reversibly suppressed by hesperetin in a concentration and voltage dependent fashion with an IC50 of 62.99?mol/L.Hesperetin significantly and negatively shifted the voltage-dependent activation and inactivation curve.Hesperetin also markedly decelerated the inactivation of Nav1.5currents and slowed the recovery from inactivation of Nav1.5 channels.Furthermore,the hesperetin-dependent blocking of Nav1.5 currents depended on the frequency.Conclusion:Hesperetin is a potent inhibitor of Nav1.5 channels that likely functions by blocking the open state and the inactived state channels.Part ?Effects of hesperetin on Ikur and INa in human atrial myocyteObjective: The current study aimed at investigating the inhibitory effects of hesperetin?HSP?on ultra-rapid delayed rectifier K+ current and voltage-gated cardiac sodium current in human atrial myocytes.Methods: The effects of hesperetin on ultra-rapid delayed rectifier K+ current and voltage-gated cardiac sodium current in enzymatically dissociated human atrial myocyteswere examined using whole-cell patch-clamp techniques.Results: Hesperetin potently and reversibly inhibited the ultra-repaid delayed K+ current?Ikur?in human atrial myocytes,which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells.Hesperetin was also found that potently and reversibly inhibited the Na+ currents?INa?in human atrial myocytes,which is in consistent with the effects of hesperetin on Nav1.5 currents in HEK 293 cells.Conclusion:Hesperetin is a potent inhibitor of Ikur and INa in human atrial myocytesConclusionIn conclusion,hesperetin is a potent inhibitorof Ikur in human atrial myocytes which is encoded by Kv1.5 gene,and the inhibition was mediated through preferential interaction with the open and inactivated states of Kv1.5 from the outside of the cell.And hesperetin is also a potent blocker of Nav1.5 channels which is mediated through interaction with both the open and inactivated states of Nav1.5 channels.However,whether the inhibition of IKur and INa by hesperetin would exert a beneficial action on atrial fibrillation needs further study.