Hidden markov model analysis of intermediate gating steps associated with the pore gate of Shaker potassium channels

Jie Zheng, L. Vankataramanan, F. J. Sigworth

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Cooperativity among the four subunits helps give rise to the remarkable voltage sensitivity of Shaker potassium channels, whose open probability changes tenfold for a 5-mV change in membrane potential. The cooperativity in these channels is thought to arise from a concerted structural transition as the final step in opening the channel. Recordings of single-channel ionic currents from certain other channel types, as well as our previous recordings from T442S mutant Shaker channels, however, display intermediate conductance levels in addition to the fully open and closed states. These sublevels might represent stepwise, rather than concerted, transitions in the final steps of channel activation. Here, we report a similar fine structure in the closing transitions of Shaker channels lacking the mutation. Describing the deactivation time course with hidden Markov models, we find that two subconductance levels are rapidly traversed during most closing transitions of chimeric, high conductance Shaker channels. The lifetimes of these levels are voltage-dependent, with maximal values of 52 and 22 μs at -100 mV, and the voltage dependences of transitions among these states suggest that they arise from equivalent conformational changes occurring in individual subunits. At least one subconductance level is found to be traversed in normal conductance Shaker channels. We speculate that voltage-dependent conformational changes in the subunits give rise to changes in a "pore gate" associated with the selectivity filter region of the channel, producing the subconductance states. As a control for the hidden Markov analysis, we applied the same procedures to recordings of the recovery from N-type inactivation in Shaker channels. These transitions are found to be instantaneous in comparison.

Original languageEnglish (US)
Pages (from-to)547-562
Number of pages16
JournalJournal of General Physiology
Volume118
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

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Shaker Superfamily of Potassium Channels
Ion Channels
Membrane Potentials
Mutation

Keywords

  • Cooperativity
  • HMM
  • Likelihood
  • Patch clamp
  • Subconductance

ASJC Scopus subject areas

  • Physiology

Cite this

Hidden markov model analysis of intermediate gating steps associated with the pore gate of Shaker potassium channels. / Zheng, Jie; Vankataramanan, L.; Sigworth, F. J.

In: Journal of General Physiology, Vol. 118, No. 5, 2001, p. 547-562.

Research output: Contribution to journalArticle

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