Tannic Acid Modulates Voltage-gated K+ Channels to Promote Neuritogenesis in Neuronal N2A Cells

In a previous report, we showed that voltage-gated K+ (Kv) Kv1 and Kv2 channels are involved in cAMP-induced neuritogenesis of mouse neuronal N2A cells. In this report, we examined the effects of tannic acid (TA) on Kv channels and neuritogenesis in N2A cells. TA (15 mu M) mildly enhanced Kv currents at -30 to -20 mV but strongly inhibited Kv currents at higher voltages, causing a preferential activation of currents at low voltages. When enhancement and suppression of Kv currents (at -20 and +70 mV, respectively) by different concentrations of TA were analyzed, TA at 4 mu M produced strong enhancement at -20 mV with relatively mild suppression at + 70 mV. TA (4 mu M) also promoted neuritogenesis; such promotion was suppressed by a Kv channel blocker tetraethylammonium ion, or a combination of hongotoxin-1 (blocker of Kv1.1), UK 78282 (blocker of Kv1.4) and guangxitoxin 1E (blocker of Kv2.1). Our results demonstrate, for the first time, TA at low concentrations could modulate Kv channels and thereby promote neuritogenesis.