Falsification of the ionic channel theory of hair cell transduction

2 years ago

Summaries

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Draws on a finding from a [Corey and Hudspeth paper](http://corey.med.harvard.edu/PDFs/1979%20Corey%20Hudspeth%20ionic.pdf) that the reversal potential of mechanotransduction current is different from the Nearnst equallibrium for $Na ^+$, and argues that this is incompatible with the idea that mechanotransduction achieved by ion channels.

Praise

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Despite some logic errors, this paper is very clear about the reasoning behind the conclusions. Example: > The contradiction presented in this paper is found in the difference between the measured reversal potential and the computed equilibrium potential using the Nernst equation.

Re: Rigor

Criticism

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The author finds a contradiction because the expected reversal potential of Na^+^ (according to the Nernst Eq.) differs from the observed reversal potential of mechanotransduction. However, he failed to take into account the opposite gradient in K^+^, which usually has a high concentration inside hair cells. This is also why neuronal receptors that are nonselective cation channels reverse around zero mV (e.g., AMPA receptors). When multiple ions are involved, one should use the Goldman-Hodgkin-Katz voltage equation, which takes into account the concentration of all ions and their relative permeability through the channel. The experiment of putting 248 mM Na^+^ in the external may be difficult because the total osmolarity of the solution would greatly exceed physiological osmolarity (and that inside the cell). However, one could double the intracellular Na^+^ (preferably by replacing K^+^). The GHK equation predicts the reversal potential to not change greatly as the reversal potential is not very sensitive to the exact gradients of each ion when they have strong opposing gradients (each of the individual ions conducts in a rectifying fashion, inward current is dominated by the ion that is in excess outside, and vice versa, the exact zero crossings of each ion don't matter much in the summed flux).

Re: Novelty

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> My prediction is that the reversal potential will remain at zero in violation of the Nernst equation and require a reevaluation of > current transduction theory. Much of the paper reads like this. So much certainty!

Re: Coolness

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A summary of which known sensory transduction pathways start with ionic conductances (touch?) and which start with G-proteins (vision, taste, smell) would have been useful and might have helped the author's case.

Re: Rigor