Dataset Information

The voltage dependence of gating currents of the neuronal CA(v)3.3 channel is determined by the gating brake in the I-II loop.

ABSTRACT: Low-voltage-activated Ca(v)3 Ca(2+) channels have an activation threshold around -60 mV, which is lower than the activation threshold of other voltage-dependent calcium channels (VDCCs). The kinetics of their activation at membrane voltages just above the activation threshold is much slower than the activation kinetics of other VDCCs. It was demonstrated recently that the intracellular loop connecting repeats I and II of all three Ca(v)3 channels contains a so-called gating brake. Disruption of this brake yields channels that activate at even more hyperpolarized potentials with significantly accelerated kinetics. We have compared gating of a wild-type Ca(v)3.3 channel and a mutated ID12 channel, in which the putative gating brake at the proximal part of the I-II loop was removed. Voltage dependence of the gating current activation was shifted by 34.6 mV towards more hyperpolarized potentials in ID12 channel. ON-charge movement was significantly faster in the ID12 channel, while the kinetics of the off-charge was not altered by the mutation. We conclude that the putative gating brake in I-II loop hinders not only the opening of the conducting pore but also the activating movement of voltage-sensing S4 segments, stabilizing the channel in its closed state.

SUBMITTER: Karmazinova M

PROVIDER: S-EPMC3310167 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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The voltage dependence of gating currents of the neuronal CA(v)3.3 channel is determined by the gating brake in the I-II loop.

Karmažínová Mária M Baumgart Joel P JP Perez-Reyes Edward E Lacinová Lubica L

Pflugers Archiv : European journal of physiology 20110223 4

Low-voltage-activated Ca(v)3 Ca(2+) channels have an activation threshold around -60 mV, which is lower than the activation threshold of other voltage-dependent calcium channels (VDCCs). The kinetics of their activation at membrane voltages just above the activation threshold is much slower than the activation kinetics of other VDCCs. It was demonstrated recently that the intracellular loop connecting repeats I and II of all three Ca(v)3 channels contains a so-called gating brake. Disruption of ...[more]

PMID: 21340458

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Project description:The mouse Slo3 gene (KCNMA3) encodes a K(+) channel that is regulated by changes in cytosolic pH. Like Slo1 subunits responsible for the Ca(2+) and voltage-activated BK-type channel, the Slo3 alpha subunit contains a pore module with homology to voltage-gated K(+) channels and also an extensive cytosolic C terminus thought to be responsible for ligand dependence. For the Slo3 K(+) channel, increases in cytosolic pH promote channel activation, but very little is known about many fundamental properties of Slo3 currents. Here we define the dependence of macroscopic conductance on voltage and pH and, in particular, examine Slo3 conductance activated at negative potentials. Using this information, the ability of a Horrigan-Aldrich-type of general allosteric model to account for Slo3 gating is examined. Finally, the pH and voltage dependence of Slo3 activation and deactivation kinetics is reported. The results indicate that Slo3 differs from Slo1 in several important ways. The limiting conductance activated at the most positive potentials exhibits a pH-dependent maximum, suggesting differences in the limiting open probability at different pH. Furthermore, over a 600 mV range of voltages (-300 to +300 mV), Slo3 conductance shifts only about two to three orders of magnitude, and the limiting conductance at negative potentials is relatively voltage independent compared to Slo1. Within the context of the Horrigan-Aldrich model, these results indicate that the intrinsic voltage dependence (z(L)) of the Slo3 closed-open equilibrium and the coupling (D) between voltage sensor movement are less than in Slo1. The kinetic behavior of Slo3 currents also differs markedly from Slo1. Both activation and deactivation are best described by two exponential components, both of which are only weakly voltage dependent. Qualitatively, the properties of the two kinetic components in the activation time course suggest that increases in pH increase the fraction of more rapidly opening channels.

Dataset Information

The voltage dependence of gating currents of the neuronal CA(v)3.3 channel is determined by the gating brake in the I-II loop.

Publications

The voltage dependence of gating currents of the neuronal CA(v)3.3 channel is determined by the gating brake in the I-II loop.

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