GABA Receptors Can Depolarize the Neuronal Membrane Potential via Quantum Tunneling of Chloride Ions: A Quantum Mathematical Study

Abstract

GABA (gamma-aminobutyric acid) receptors represent the major inhibitory receptors in the nervous system and their inhibitory effects are mediated by the influx of chloride ions that tends to hyperpolarize the resting membrane potential. However, GABA receptors can depolarize the resting membrane potential and thus can also show excitatory effects in neurons. The major mechanism behind this depolarization is mainly attributed to the accumulation of chloride ions in the intracellular compartment. This accumulation leads to increase in the intracellular chloride concentration and depolarize the Nernst potential of chloride ions. When the membrane potential is relatively hyperpolarized, this will result in a chloride efflux instead of influx trying to reach their depolarized equilibrium potential. Here, we propose different mechanism based on a major consequence of quantum mechanics, which is quantum tunneling. The quantum tunneling model of ions is applied on GABA receptors and their corresponding chloride ions to show how chloride ions can depolarize the resting membrane potential. The quantum model states that intracellular chloride ions have higher quantum tunneling probability than extracellular chloride ions. This is attributed to the discrepancy in the kinetic energy between them. At physiological parameters, the quantum tunneling is negligible to the degree that chloride ions cannot depolarize the membrane potential. Under certain conditions such as early neuronal development, gain-of-function mutations, stroke and trauma that can lower the energy barrier of the closed gate of GABA receptors, the quantum tunneling is enhanced so that the chloride ions can depolarize the resting membrane potential. The major unique feature of the quantum tunneling mechanism is that the net efflux of chloride ions is attained without the need for intracellular accumulation of chloride ions as long as the energy barrier of the gate is reduced but still higher than the kinetic energy of the chloride ion as a condition for quantum tunneling to take place.

Gate control of sensory neurotransmission in peripheral ganglia by proprioceptive sensory neurons

“… 19–21 Another confounding factor is the theoretical framework of membrane depolarization mediated by GABA receptors through quantum tunnelling; however, the work in our study was not focused on membrane excitability of individual cells, but rather in vivo outcomes that capture the polysynaptic constitution of pain behaviour. 22 Importantly, our data demonstrate that the robust effect of GABA receptor antagonism on enhanced nocifensive responses in littermate mice following PGE 2 administration is lost in the absence of PV neurons in DTA mice ( Fig. 3I ).…”

Golden Ratio Information for Neural Spike Code

“…The model looks exactly the same under the transformation gr = 1 and ψ = 1/ϕ, the resistance characteristics, leading to a unique model for any given neuron, rather than innumerable ad hoc models as conventionally is the case. This model then predicts that the phenomenon of spontaneous firing of individual ion channels ( [9,10]) by ways of quantum tunneling ( [11]) is both sufficient and necessary, marking the first transition from the quantum realm to the microscopic world in neuronal modeling. The model automatically gives rise to different time scales for ion and protein channels, permitting dramatic simplifications in dimensional reduction.…”

“…This is due to a phenomenon, referred to as spike frequency adaptation ( [4,5]), for neural models. Let τ * be the same parameter as in (11) that is the average spike-burst period for k ≥ 2 and τ k = τ * k for k ≥ 2.…”

The complexities of ligand/receptor interactions: Exploring the role of molecular vibrations and quantum tunnelling

“…The only LGIC for which tunneling has been invoked to account for its function is a type of GABA‐A receptor, where chloride tunneling across the cell membrane was proposed. [ 111 ] Still, this latter work proposed tunneling for the result of the binding phenomenon (ion conductance), not the binding and function relationship; it did not propose a link between binding and the receptor's conformational change responsible for its physiology.…”