Rhynchophylline from Uncaria rhynchophylla Functionally Turns Delayed Rectifiers into A-Type K⁺ Channels

Abstract

Rhynchophylline (1), a neuroprotective agent isolated from the traditional Chinese medicinal herb Uncaria rhynchophylla, was shown to affect voltage-gated K(+) (Kv) channel slow inactivation in mouse neuroblastoma N2A cells. Extracellular 1 (30 microM) accelerated the slow decay of Kv currents and shifted the steady-state inactivation curve to the left. Intracellular dialysis of 1 did not accelerate the slow current decay, suggesting that this compound acts extracellularly. In addition, the percent blockage of Kv currents by this substance was independent of the degree of depolarization and the intracellular K(+) concentration. Therefore, 1 did not appear to directly block the outer channel pore, with the results obtained suggesting that it drastically accelerated Kv channel slow inactivation. Interestingly, 1 also shifted the activation curve to the left. This alkaloid also strongly accelerated slow inactivation and caused a left shift of the activation curve of Kv1.2 channels heterologously expressed in HEK293 cells. Thus, this compound functionally turned delayed rectifiers into A-type K(+) channels.

Anti-inflammatory effects of rhynchophylline and isorhynchophylline in mouse N9 microglial cells and the molecular mechanism

“…Activated microglial cells also express outward K + channels, which selectively involve in the activation of signalling cascades, such as superoxide production or iNOS expression [39,40]. The blocking effects of RIN and IRN on Ca 2+ and K + channels was well studied in rat ventricular myocytes and mouse neuroblastoma N2A cells [41][42][43][44]. Thus, the modulating effects of RIN and IRN on LPS-induced [Ca 2+ ]i and K + current changes in microglial cells need to be further investigated.…”

Antihypertensive and neuroprotective activities of rhynchophylline: The role of rhynchophylline in neurotransmission and ion channel activity

“…This alkaloid also strongly accelerated slow inactivation and caused a leftward shift of the activation curve of the voltage-gated K + channel Kv1.2, which was heterologously expressed in HEK293 cells. Thus, rhynchophylline functionally turned delayed rectifiers into A-type K + channels (Chou et al, 2009).…”

Control of ionic selectivity by a pore helix residue in the Kv1.2 channel

“…In previous reports, we used HEK293 cells for expression of Kv1.2 WT channels [10,11]. However, the expression of Kv1.2 V370G was much poorer than the WT.…”