Application of TELC model to neuroscience: Better elucidation for neural stimulation by touch

Abstract

The 2021 Nobel Prize in Physiology or Medicine was recently awarded to David Julius and Ardem Patapoutian “for their discoveries of receptors for temperature and touch”. It is well established that touch receptors (PIEZO) provide sensory inputs to inform the brain about objects in our environment. However, exactly how the transient ion transport activity of touch receptors could stimulate action potential firing seems still not entirely clear. In this article, the latest transmembrane-electrostatically localized protons/cations charges (TELC) theory is employed to better understand neural stimulation and action potential that we have recently identified as the voltage contributed by TELC at a neural liquid-membrane interface in a neural cell. The TELC density at the resting membrane potential of −70 mV is now calculated to be 3900 (protons + cations) per μm2 on extracellular membrane surface. At the stimulation threshold level (−55 mV), the TELC density is calculated to be 3100 (protons + cations) per μm2. Accordingly, the neural stimulation by touch can now be better understood by analyzing PIEZO ion conduction and TELC activity. The response time from PIEZO channel ion conduction activities to reduce the TELC density to the stimulation level of 3100 TELC per μm2 for action potential firing was calculated for the first time. The activities of a single or a few PIEZO channels may be sufficient to generate a “graded potential” to trigger an action potential spike firing. With a high number (200~300) of PIEZO channels activated by touch, it can generate the required “graded potential” to reach the stimulation threshold level (−55 mV) within 0.3 ms. Real-time action potential (Vt) with PIEZO mechanically-activated stimulation by touch is now, mathematically explained through a novel integral equation (Vt=-1/C ∫0t I(t)dt+ V0) of the net time-dependent transmembrane ion current I(t), which is fundamentally important to neuroscience.