Electrostatic interaction in the NH2-terminus accelerates inactivation of the Kv1.4 channel |
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Authors: | Zhuo Fan Li-jun Bi Gang Jin Zhi Qi |
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Institution: | a National Laboratory of Biomacromolecules and State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, CAS, 15 Datun Rd, Beijing 100101, Chinab Department of Physiology, Medical College of Xiamen University, 168 Daxue Rd, Xiamen 361005, Chinac Graduate University of Chinese Academy of Sciences, 19A Yuquan Rd, Beijing 100039, China |
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Abstract: | Inactivation of potassium channels plays an important role in shaping the electrical signalling properties of nerve and muscle cells. While it has been assumed that the rapid inactivation of the Kv1.4 channel is controlled by a “ball and chain” inactivation mechanism, the chain structure of the channel has not been well defined. Here, by conducting electrophysiological studies on variants containing mutations of the positively charged and negatively charged segments of the NH2-terminal of the channel protein, we show that neutralization or deletion of the positively charged segment (residues 83-98) significantly slowed the inactivation process. Replacement of this positively charged segment with the negatively charged segment (residues 123-137), and vice versa, so that both segments were simultaneously positively or negatively charged, also slowed the inactivation process. Furthermore, the inactivation process was not changed when the positively charged and the negatively charged segments were interchanged. In contrast, the voltage dependence of activation and inactivation of the channels was not significantly altered by these mutants. These results indicate that the electrostatic interaction between the positively and negatively charged segments plays a critical role in the inactivation process of the Kv1.4 channel. Taken together, we propose that the electrostatic interaction accelerates the inactivation of the Kv1.4 channel by making it easier for the inactivation ball to access its binding site. |
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Keywords: | Inactivation Kv1 4 channel Ball and chain model Electrostatic interaction |
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