Background and Objective: Madecassic Acid (MA) is well known to induce neurite elongation.
However, its correlation with the expression of fast transient potassium (AKv) channels during
neuronal development has not been well studied. Therefore, the present study was designed to investigate
the effects of MA on the modulation of AKv channels during neurite outgrowth.
Methods: Neurite outgrowth was measured with morphometry software, and Kv4 currents were recorded
by using the patch clamp technique.
Results: The ability of MA to promote neurite outgrowth is dose-dependent and was blocked by using
the mitogen/extracellular signal-regulated kinase (MEK) inhibitor U0126. MA reduced the peak current
density and surface expression of the AKv channel Kv4.2 with or without the presence of NaN3.
The surface expression of Kv4.2 channels was also reduced after MA treatment of growing neurons.
Ethylene glycol tetraacetic acid (EGTA) and an N-methyl-D-aspartate (NMDA) receptor blocker,
MK801 along with MA prevented the effect of MA on neurite length, indicating that calcium entry
through NMDA receptors is necessary for MA-induced neurite outgrowth.
Conclusion: The data demonstrated that MA increased neurite outgrowth by internalizing AKv channels
in neurons. Any alterations in the precise density of ion channels can lead to deleterious consequences
on health because it changes the electrical and mechanical function of a neuron or a cell.
Modulating ion channel’s density is exciting research in order to develop novel drugs for the therapeutic
treatment of various diseases of CNS.