鉤藤鹼是從傳統中國草藥鉤藤中，所萃取出來具有神經保護作用的成分。我們以小鼠神經母瘤細胞N2A細胞膜上的電位調控鉀離子通道(Kv channel)為實驗材料，發現鉤藤鹼能影響Kv通道的慢性鈍化過程。當細胞外加入30 μM的鉤藤鹼，能加速Kv電流的慢性鈍化過程並左移穩定態鈍化曲線，因此能抑制細胞膜去極化時所誘發的鉀離子外流。當細胞內加入鉤藤鹼時，不會加快慢性鈍化過程，所以我們推測鉤藤鹼作用在Kv通道細胞外的部分，而非細胞內。此外，由於使用不同去極化的膜電位刺激以及改變細胞內的鉀離子濃度，都不影響鉤藤鹼抑制鉀離子外流的程度。因此，我們認為鉤藤鹼似乎不是一個Kv通道外孔之直接阻斷劑。另外很有趣的一點是，雖然我們推測這藥物是作用在Kv通道細胞外的部分，但它卻會影響細胞內活化閘門的活化曲線，使之左移。在另外的實驗中，我們將Kv1.2通道異源性表達在人類胚胎腎臟細胞株HEK293上，發現鉤藤鹼也會加速Kv1.2通道的慢性鈍化並左移活化曲線。因此，我們認為鉤藤鹼能作用在Kv通道上，並且功能性地轉換延遲整流型鉀離子通道成為A型鉀離子通道。
Rhynchophylline (rhyn), 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 rhyn (30 μM) accelerated the slow decay of Kv currents and shifted the steady-state inactivation curve to the left. Intracellular dialysis of rhyn 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, rhyn did not appear to directly block the outer channel pore, with the results obtained suggesting that it drastically accelerated Kv channel slow inactivation. Interestingly, rhyn 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.
