State-Dependent Inactivation of the α1g T-Type Calcium Channel
Open Access
- 1 August 1999
- journal article
- Published by Rockefeller University Press in The Journal of general physiology
- Vol. 114 (2) , 185-202
- https://doi.org/10.1085/jgp.114.2.185
Abstract
We have examined the kinetics of whole-cell T-current in HEK 293 cells stably expressing the α1G channel, with symmetrical Na+i and Na+o and 2 mM Ca2+o. After brief strong depolarization to activate the channels (2 ms at +60 mV; holding potential −100 mV), currents relaxed exponentially at all voltages. The time constant of the relaxation was exponentially voltage dependent from −120 to −70 mV , but . This suggests a mixture of voltage-dependent deactivation (dominating at very negative voltages) and nearly voltage-independent inactivation. Inactivation measured by test pulses following that protocol was consistent with open-state inactivation. During depolarizations lasting 100–300 ms, inactivation was strong but incomplete (∼98%). Inactivation was also produced by long, weak depolarizations , which could not be explained by voltage-independent inactivation exclusively from the open state. Recovery from inactivation was exponential and fast , but weakly voltage dependent. Recovery was similar after 60-ms steps to −20 mV or 600-ms steps to −70 mV, suggesting rapid equilibration of open- and closed-state inactivation. There was little current at −100 mV during recovery from inactivation, consistent with ≤8% of the channels recovering through the open state. The results are well described by a kinetic model where inactivation is allosterically coupled to the movement of the first three voltage sensors to activate. One consequence of state-dependent inactivation is that α1G channels continue to inactivate after repolarization, primarily from the open state, which leads to cumulative inactivation during repetitive pulses.Keywords
This publication has 60 references indexed in Scilit:
- Properties of Ba2+ currents arising from human α1E and α1Eβ3 constructs expressed in HEK293 cells: physiology, pharmacology, and comparison to native T-type Ba2+ currentsNeuropharmacology, 1998
- Known Calcium Channel α1 Subunits Can Form Low Threshold Small Conductance Channels with Similarities to Native T-Type ChannelsNeuron, 1998
- The ‘window’ component of the low threshold Ca2+ current produces input signal amplification and bistability in cat and rat thalamocortical neuronesThe Journal of Physiology, 1997
- Na+ channels must deactivate to recover from inactivationNeuron, 1994
- Structure and Functional Expression of a Member of the Low Voltage-Activated Calcium Channel FamilyScience, 1993
- Mechanism of gating of T-type calcium channels.The Journal of general physiology, 1990
- State-dependent inactivation of K+ currents in rat type II alveolar epithelial cells.The Journal of general physiology, 1990
- Sodium channel gating in clonal pituitary cells. The inactivation step is not voltage dependent.The Journal of general physiology, 1989
- Classes of Calcium Channels in Vertebrate CellsAnnual Review of Physiology, 1989
- Two Distinct Populations of Calcium Channels in a Clonal Line of Pituitary CellsScience, 1985