Mechanism of inactivation gating of human T-type (low-voltage activated) calcium channels

Don E. Burgess, Oscar Crawford, Brian P. Delisle, Jonathan Satin

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Recovery from inactivation of T-type Ca channels is slow and saturates at moderate hyperpolarizing voltage steps compared with Na channels. To explore this unique kinetic pattern we measured gating and ionic currents in two closely related isoforms of T-type Ca channels. Gating current recovers from inactivation much faster than ionic current, and recovery from inactivation is much more vortage dependent for gating current than for ionic current. There is a lag in the onset of gating current recovery at -80 mV, but no lag is discernible at -120 mV. The delay in recovery from inactivation of ionic current is much more evident at all voltages. The time constant for the decay of off gating current is very similar to the time constant of deactivation of open channels (ionic tail current), and both are strongly voltage dependent over a wide voltage range. Apparently, the development of inactivation has little influence on the initial deactivation step. These results suggest that movement of gating charge occurs for inactivated states very quickly. In contrast, the transitions from inactivated to available states are orders of magnitude slower, not voltage dependent, and are rate limiting for ionic recovery. These findings support a deactivation-first path for T-type Ca channel recovery from inactivation. We have integrated these concepts into an eight-state kinetic model, which can account for the major characteristics of T-type Ca channel inactivation.

Original languageEnglish
Pages (from-to)1894-1906
Number of pages13
JournalBiophysical Journal
Issue number4
StatePublished - 2002

Bibliographical note

Funding Information:
This work was supported by AHA9806307 (D.B.) and National Institutes of Health HL63416 (J.S.).

ASJC Scopus subject areas

  • Biophysics


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