Contrasting the roles of the I-II loop gating brake in Ca3.1 and Ca3.3 calcium channels.
- Resource Type
- Article
- Authors
- Karmažínová, Mária; Jašková, Katarína; Griac, Peter; Perez-Reyes, Edward; Lacinová, Ľubica
- Source
- Pflügers Archiv: European Journal of Physiology. Dec2015, Vol. 467 Issue 12, p2519-2527. 9p.
- Subject
- *CALCIUM channels
*ACTIVATION (Chemistry)
*INTRACELLULAR calcium
*LOW voltage systems
*BODY movement
- Language
- ISSN
- 0031-6768
Low-voltage-activated Ca3 channels are distinguished among other voltage-activated calcium channels by the most negative voltage activation threshold. The voltage dependence of current activation is virtually identical in all three Ca3 channels while the current kinetics of the Ca3.3 current is one order slower than that of the Ca3.1 and Ca3.2 channels. We have analyzed the voltage dependence and kinetics of charge (Q) movement in human recombinant Ca3.3 and Ca3.1 channels. The voltage dependence of voltage sensor activation (Q-V) of the Ca3.3 channel was significantly shifted with respect to that of the Ca3.1 channel by +18.6 mV and the kinetic of Q activation in the Ca3.3 channel was significantly slower than that of the Ca3.1 channel. Removal of the gating brake in the intracellular loop connecting repeats I and II in the Ca3.3 channel in the ID12 mutant channel shifted the Q-V relation to a value even more negative than that for the Ca3.1 channel. The kinetic of Q activation was not significantly different between ID12 and Ca3.1 channels. Deletion of the gating brake in the Ca3.1 channel resulted in a GD12 channel with the voltage dependence of the gating current activation significantly shifted toward more negative potentials. The Q kinetic was not significantly altered. ID12 and GD12 mutants did not differ significantly in voltage dependence nor in the kinetic of voltage sensor activation. In conclusion, the putative gating brake in the intracellular loop connecting repeats I and II controls the gating current of the Ca3 channels. We suggest that activation of the voltage sensor in domain I is limiting both the voltage dependence and the kinetics of Ca3 channel activation. [ABSTRACT FROM AUTHOR]