Cytoskeleton disruption affects Kv2.1 channel function and its modulation by PIP2
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Voltage-gated potassium channels are expressed in a wide variety of excitable and non-excitable cells and regulate numerous cellular functions. The activity of ion channels can be modulated by direct interaction or/and functional coupling with other proteins including auxiliary subunits, scaffold proteins and the cytoskeleton. Here, we evaluated the influence of the actin-based cytoskeleton on the Kv2.1 channel using pharmacological and electrophysiological methods. We found that disruption of the actin-based cytoskeleton by latrunculin B resulted in the regulation of the Kv2.1 inactivation mechanism; it shifted the voltage of half-maximal inactivation toward negative potentials by approximately 15 mV, accelerated the rate of closed-state inactivation, and delayed the recovery rate from inactivation. The actin cytoskeleton stabilizing agent phalloidin prevented the hyperpolarizing shift in the half-maximal inactivation potential when co-applied with latrunculin B. Additionally, PIP2 depletion (a strategy that regulates Kv2.1 inactivation) after cytoskeleton disruption does not regulate further the inactivation of Kv2.1, which suggests that both factors could be regulating the Kv2.1 channel by a common mechanism. In summary, our results suggest a role for the actin-based cytoskeleton in regulating Kv2.1 channels.
KeywordsKv channels Cytoskeleton Latrunculin B Phalloidin PIP2 Patch clamp
We thank Xóchitl Ordaz Ruiz for technical assistance.
M.D-R.: performed experiments, contributed to discussion, wrote/reviewed/edited manuscript. A.A.R-M.: conceived the project and contributed to discussion, wrote/reviewed/edited manuscript.
This work was supported by SEP-CONACYT grants CB-157245 and CB-284443 (to A.A.R-M.) and CONACYT-FDC 2016-01-1995. M.D-R was supported by a Student Fellowship from CONACYT, México (374053).
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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