TY - JOUR

T1 - The thermodynamic soliton theory of the nervous impulse and possible medical implications

AU - Heimburg, T.

PY - 2022/5/28

Y1 - 2022/5/28

N2 - The textbook picture of nerve activity is that of a propagating voltage pulse driven by electrical currents through ion channel proteins, which are gated by changes in voltage, temperature, pressure or by drugs. All function is directly attributed to single molecules. We show that this leaves out many important thermodynamic couplings between different variables. A more recent alternative picture for the nerve pulse is of thermodynamic nature. It considers the nerve pulse as a soliton, i.e., a macroscopic excited region with properties that are influenced by thermodynamic variables including voltage, temperature, pressure and chemical potentials of membrane components. All thermodynamic variables are strictly coupled. We discuss the consequences for medical treatment in a view where one can compensate a maladjustment of one variable by adjusting another variable. For instance, one can explain why anesthesia can be counteracted by hydrostatic pressure and decrease in pH, suggest reasons why lithium over-dose may lead to tremor, and how tremor is related to alcohol intoxication. Lithium action as well as the effect of ethanol and the anesthetic ketamine in bipolar patients may fall in similar thermodynamic patterns. Such couplings remain obscure in a purely molecular picture. Other fields of application are the response of nerve activity to muscle stretching and the possibility of neural stimulation by ultrasound.

AB - The textbook picture of nerve activity is that of a propagating voltage pulse driven by electrical currents through ion channel proteins, which are gated by changes in voltage, temperature, pressure or by drugs. All function is directly attributed to single molecules. We show that this leaves out many important thermodynamic couplings between different variables. A more recent alternative picture for the nerve pulse is of thermodynamic nature. It considers the nerve pulse as a soliton, i.e., a macroscopic excited region with properties that are influenced by thermodynamic variables including voltage, temperature, pressure and chemical potentials of membrane components. All thermodynamic variables are strictly coupled. We discuss the consequences for medical treatment in a view where one can compensate a maladjustment of one variable by adjusting another variable. For instance, one can explain why anesthesia can be counteracted by hydrostatic pressure and decrease in pH, suggest reasons why lithium over-dose may lead to tremor, and how tremor is related to alcohol intoxication. Lithium action as well as the effect of ethanol and the anesthetic ketamine in bipolar patients may fall in similar thermodynamic patterns. Such couplings remain obscure in a purely molecular picture. Other fields of application are the response of nerve activity to muscle stretching and the possibility of neural stimulation by ultrasound.

KW - Nerves

KW - Action potential

KW - Hodgkin -Huxley model

KW - Anesthesia

KW - Ion channels

KW - Thermodynamic couplings

KW - LIPID-MEMBRANES

KW - INTRACELLULAR PH

KW - ION CHANNELS

KW - PHASE-TRANSITION

KW - TEMPERATURE-DEPENDENCE

KW - CONDUCTION-VELOCITY

KW - MELTING TRANSITION

KW - HEAT-PRODUCTION

KW - IN-VITRO

KW - MUSCLE

U2 - 10.1016/j.pbiomolbio.2022.05.007

DO - 10.1016/j.pbiomolbio.2022.05.007

M3 - Review

C2 - 35640761

VL - 173

SP - 24

EP - 35

JO - Progress in Biophysics and Molecular Biology

JF - Progress in Biophysics and Molecular Biology

SN - 0079-6107

ER -