Bubbles, Gating, and Anesthetics in Ion Channels

¹ Max-Planck Institut für Metallforschung, Heisenbergstraße 3, D-70569 Stuttgart, Germany
² Rush University Medical Center, 1653 W Congress Parkway, Chicago IL 60612
³ Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FL 3
⁴ Rush University Medical Center, 1653 W Congress Parkway, Chicago IL 60612 USA

^* To whom correspondence should be addressed. E-mail: beisenbe{at}rush.edu.

Submitted on August 27, 2007
Revised on September 27, 2007
Accepted on 16 January 2008

	Abstract

We suggest that bubbles are the bistable hydrophobic gates responsible for the on-off transitions of single channel currents. In this view, many types of channels gate by the same physical mechanism -- dewetting by capillary evaporation -- but different types of channels use different sensors to modulate hydrophobic properties of the channel wall and thereby trigger and control bubbles and gating. Spontaneous emptying of channels has been seen in many simulations. Because of the physics involved, such phase transitions are inherently sensitive, unstable threshold phenomena difficult to simulate reproducibly and thus convincingly. We present a thermodynamic analysis of a bubble gate using morphometric density functional theory of classical (not quantum) mechanics. Thermodynamic analysis of phase transitions is generally more reproducible and less sensitive to details than simulations. Anesthetic actions of inert gases -- and their interactions with hydrostatic pressure (e.g., nitrogen narcosis) -- can be easily understood by actions on bubbles. A general theory of gas anesthesia may involve bubbles in channels. Only experiments can show whether, or when, or which channels actually use bubbles as hydrophobic gates: direct observation of bubbles in channels are needed. Existing experiments show thin gas layers on hydrophobic surfaces in water and suggest that bubbles nearly exist in bulk water.

Key Words: anesthesia, bubble, gating, hydrophobic, xenon

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