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Gating kinetics of the alpha1I T-type calcium channel.

Frazier CJ, Serrano JR, George EG, Yu X, Viswanathan A, Perez-Reyes E, Jones SW - J. Gen. Physiol. (2001)

Bottom Line: We found several kinetic differences between alpha1G and alpha1I, including some properties that at first appear qualitatively different.Nearly all of the rate constants in the model are 5-12-fold slower for alpha1I, but the microscopic rate for channel closing is fourfold faster.This suggests that T-channels share a common gating mechanism, but with considerable quantitative variability.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA.

ABSTRACT
The alpha1I T-type calcium channel inactivates almost 10-fold more slowly than the other family members (alpha1G and alpha1H) or most native T-channels. We have examined the underlying mechanisms using whole-cell recordings from rat alpha1I stably expressed in HEK293 cells. We found several kinetic differences between alpha1G and alpha1I, including some properties that at first appear qualitatively different. Notably, alpha1I tail currents require two or even three exponentials, whereas alpha1G tails were well described by a single exponential over a wide voltage range. Also, closed-state inactivation is more significant for alpha1I, even for relatively strong depolarizations. Despite these differences, gating of alpha1I can be described by the same kinetic scheme used for alpha1G, where voltage sensor movement is allosterically coupled to inactivation. Nearly all of the rate constants in the model are 5-12-fold slower for alpha1I, but the microscopic rate for channel closing is fourfold faster. This suggests that T-channels share a common gating mechanism, but with considerable quantitative variability.

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Related in: MedlinePlus

Three components of tail currents at −40 mV, shown on a log-log scale. The data record is from the middle panel of Fig. 5 B. The dashed curves are the three fitted exponential components, the offset, and the sum of all components.
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Figure 6: Three components of tail currents at −40 mV, shown on a log-log scale. The data record is from the middle panel of Fig. 5 B. The dashed curves are the three fitted exponential components, the offset, and the sum of all components.

Mentions: The three exponential components were most clearly demonstrated in tail currents at −40 mV (Fig. 6), where the time constants were well separated, and the amplitudes were comparable and thus easily detectable. In seven cells, the time constants were 1.5 ± 0.2, 27 ± 4, and 118 ± 14 ms, with relative amplitudes 0.34 ± 0.04, 0.20 ± 0.01, and 0.43 ± 0.03, respectively (offset 0.026 ± 0.004), including three cells examined with no Mg2+o.


Gating kinetics of the alpha1I T-type calcium channel.

Frazier CJ, Serrano JR, George EG, Yu X, Viswanathan A, Perez-Reyes E, Jones SW - J. Gen. Physiol. (2001)

Three components of tail currents at −40 mV, shown on a log-log scale. The data record is from the middle panel of Fig. 5 B. The dashed curves are the three fitted exponential components, the offset, and the sum of all components.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2233834&req=5

Figure 6: Three components of tail currents at −40 mV, shown on a log-log scale. The data record is from the middle panel of Fig. 5 B. The dashed curves are the three fitted exponential components, the offset, and the sum of all components.
Mentions: The three exponential components were most clearly demonstrated in tail currents at −40 mV (Fig. 6), where the time constants were well separated, and the amplitudes were comparable and thus easily detectable. In seven cells, the time constants were 1.5 ± 0.2, 27 ± 4, and 118 ± 14 ms, with relative amplitudes 0.34 ± 0.04, 0.20 ± 0.01, and 0.43 ± 0.03, respectively (offset 0.026 ± 0.004), including three cells examined with no Mg2+o.

Bottom Line: We found several kinetic differences between alpha1G and alpha1I, including some properties that at first appear qualitatively different.Nearly all of the rate constants in the model are 5-12-fold slower for alpha1I, but the microscopic rate for channel closing is fourfold faster.This suggests that T-channels share a common gating mechanism, but with considerable quantitative variability.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA.

ABSTRACT
The alpha1I T-type calcium channel inactivates almost 10-fold more slowly than the other family members (alpha1G and alpha1H) or most native T-channels. We have examined the underlying mechanisms using whole-cell recordings from rat alpha1I stably expressed in HEK293 cells. We found several kinetic differences between alpha1G and alpha1I, including some properties that at first appear qualitatively different. Notably, alpha1I tail currents require two or even three exponentials, whereas alpha1G tails were well described by a single exponential over a wide voltage range. Also, closed-state inactivation is more significant for alpha1I, even for relatively strong depolarizations. Despite these differences, gating of alpha1I can be described by the same kinetic scheme used for alpha1G, where voltage sensor movement is allosterically coupled to inactivation. Nearly all of the rate constants in the model are 5-12-fold slower for alpha1I, but the microscopic rate for channel closing is fourfold faster. This suggests that T-channels share a common gating mechanism, but with considerable quantitative variability.

Show MeSH
Related in: MedlinePlus