Depolarization and hyperpolarization

Lillie (1923) argued that electrical factors are of great importance in determining the properties of living plasma membranes. In his account, an influence that depolarizes the surface causes stimulation, and stimulation is attended with an increase of permeability.¹ Child (1924) summarized Lillie's experiments as showing that excitation involves greater permeability to negative ions, so that the membrane is more or less completely depolarized.² Child reported that Lillie did not say whether the chemical reaction, a colloidal change or something else is the primary effect of depolarization.³ Child added that this made little difference, since the whole series is mutually related.³

Crile (1926) used the word in nearly the opposite sense. He compared living tissue to a battery that is exhausted when its plates polarize. In his scheme, work polarizes and rest depolarizes.⁴ He supposed that the heart takes seventy to ninety short naps a minute and is kept depolarized, or rested, as it works.⁴ For Crile, then, depolarization marked sleep. For Lillie it accompanied excitation.¹⁴ The two authors do not agree on what the term means physiologically, though both treat it as a change in electrical state.

Sundelacruz, Levin and Kaplan (2008) tested human mesenchymal stem cells. Two treatments that depolarize by different means suppressed differentiation markers, while hyperpolarizing potassium channel openers raised bone-related gene expression. The authors therefore described membrane potential as an instructive determinant of differentiation state.⁵ Perathoner and colleagues (2014) found that hyperpolarization from a potassium channel mutation can lead to fin overgrowth. They could not exclude a secondary depolarization in surrounding tissue. They cited Xenopus work in which regenerating tails are first depolarized and then hyperpolarize, and in which blocking V-ATPase impairs proliferation and regeneration.⁶

Silver and Nelson (2018) reviewed results that point both ways. Hyperpolarizing treatments inhibited tumor formation, yet depolarized regions in bisected planaria produced ectopic heads, not tumors. Hyperpolarizing the worms after amputation inhibited head regeneration.⁷ In Xenopus, they reported, hyperpolarized regions were critical for eye development.⁷ Pare, Martyniuk and Levin (2017) found that depolarization of the host increased resistance to infection and hyperpolarization decreased it.⁸ Blackiston and colleagues (2015) concluded that hyperinnervation depends on depolarization, however it is produced, not on a particular chloride channel.⁹