Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 203K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JGP Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Serrano, J. R. Articles by Jones, S. W. Search for Related Content PubMed PubMed Citation Articles by Serrano, J. R. Articles by Jones, S. W. Social Bookmarking                            What's this?

Original Article

State-Dependent Inactivation of the 1g T-Type Calcium Channel

^a From the Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106
^b Department of Physiology, Loyola University Medical Center, Maywood, Illinois 60153
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106.Fax: 216-368-3952;

swj{at}po.cwru.edu

We have examined the kinetics of whole-cell T-current in HEK 293 cells stably expressing the 1G 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 1G channels continue to inactivate after repolarization, primarily from the open state, which leads to cumulative inactivation during repetitive pulses.

Key Words: T-channel • cumulative inactivation • recovery from inactivation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. W. Jones Commentary: A Plausible Model J. Gen. Physiol., August 1, 1999; 114(2): 271 - 275. [Full Text] [PDF]

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents