Key result
Paclitaxel dose-dependently inhibits Kv2.1 K+ current in H9c2 cells with an IC50 of 1.1 µM.
Why the study?
Does paclitaxel inhibit Kv2.1 K+ current in H9c2 cells?
Does paclitaxel inhibit Kv2.1 K+ current in H9c2 cells?
Effect estimate: IC50 1.1 µM
p-value: p=<0.01
Paclitaxel acts as an open channel blocker of Kv2.1 in rat cardiac myocytes, providing a potential mechanism for its cardiotoxic and neurotoxic adverse effects.
Hypothesis-generating for paclitaxel cardiotoxicity via Kv2.1 blockade; human studies required before any clinical relevance.
Using the whole-cell voltage clamp technique, we investigated the effect of paclitaxel, an anticancer agent which promotes microtubule formation, on K(+) current in H9c2 cells originated from rat embryonic cardiac myocytes. Paclitaxel inhibited Kv2.1 voltage-dependent K(+) current (IKur) with ultra-rapidly activating and slowly inactivating kinetics in a concentration-dependent manner. The inhibitory effect of paclitaxel on IKur was time-dependent and more marked at 200 ms after the onset than at the beginning of the depolarizing pulse. The IC50 value of paclitaxel was 1.1 µM at 200 ms. The time-dependent inhibition suggests that paclitaxel might be an open channel blocker of Kv2.1. This inhibition of Kv2.1 may be involved in the adverse effects of paclitaxel on cardiac and neuronal cells.
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Kitamura et al. (2015) studied In vitro (H9c2 cells). Paclitaxel vs. Control (absence of paclitaxel) was evaluated on Inhibition of Kv2.1 voltage-dependent K+ current (IKur) at 200 ms (IC50 1.1 µM, p=<0.01). Paclitaxel inhibited Kv2.1 voltage-dependent K+ current in H9c2 cells in a concentration- and time-dependent manner, with an IC50 of 1.1 µM at 200 ms.
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