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

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2009-05, Vol.72 (5), p.830-834
• Main Authors: Chou, Chun-Hsiao, Gong, Chi-Li, Chao, Chia-Chia, Lin, Chia-Huei, Kwan, Chiu-Yin, Hsieh, Ching-Liang, Leung, Yuk-Man
• Format: Article
• Language: English
• Subjects: alkaloids; Animals; Biological and medical sciences; cell lines; chemical structure; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - isolation & purification; Drugs, Chinese Herbal - pharmacology; electrophysiology; General pharmacology; Humans; inactivation; Indole Alkaloids - chemistry; Indole Alkaloids - isolation & purification; Indole Alkaloids - pharmacology; K+ current; Kv1.2 Potassium Channel - drug effects; Medical sciences; medicinal plants; Mice; Molecular Structure; neoplasms; neuroblastoma cells; neurons; Neuroprotective Agents - chemistry; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; neuroprotective effect; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; potassium channels; Uncaria - chemistry; Uncaria rhynchophylla; voltage-gated K+ channels
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np800729q

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 μM) 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.