Biology subjects

Mazar, M.

Publications and source records attributed to Mazar, M..

3 recordsLinked to original sources

bioRxiv2026

Direct analytical estimation of thermodynamic parameters of thermo-TRP channels

A subset of Transient Receptor Potential (TRP) channels display very steep temperature dependences and play key roles in thermosensation. To characterize the properties of these thermoTRP channels, two-state close-open gating models were developed for TRPM8, TRPV1, TRPM4, TRPM5, TRPA1 and TRPM3. In this study, we met the recurrent challenge of finding an initial set of model parameters enabling effective convergence during data fitting procedures. We performed algebraic calculations to derive equations for all gating model parameters as functions of key features of thermoTRP channel data obtained from patch-clamp experiments. We used a minimal set of experimental data: the steady-state open probability and time constant of current relaxation as functions of the membrane potential determined at two temperatures. Specifically, we could express the electric distance of the gating charge and the enthalpy and entropy changes associated with the gating transitions, as functions of the voltages for half-maximal activation, the voltages for maximal time constant of current relaxation and the maximal time constant. Our results provide a method to analytically estimate an initial set thermoTRP thermodynamic parameters enabling robust subsequent nonlinear global data fitting. This approach facilitates quantitative analysis of channel thermodynamics, and has potential applications to more complex gating models, and to the study of permeation, block and other ion channel gating mechanisms.

biophysics↗

bioRxiv2026

Tactile and pain mechanical sensitivity of the human hand

The human hand has a refined mechanical sensitivity, allowing it to play crucial roles in tactile exploration and object manipulation. Despite its fundamental and clinical relevance, a comprehensive characterization of mechanical sensitivity across the human palm is still lacking. Here, we mapped the spatial distribution of innocuous and noxious mechanical sensitivity across the palmar surface of the human hand. We examined 66 hands from 33 healthy adults, dividing the palm into 27 areas, in each of which we measured the mechanical detection threshold, the mechanical pain threshold and the pain intensity evoked by a standard 300 g pinprick stimulus. We found distal areas (i.e., fingertips) to exhibit higher tactile sensitivity than proximal areas (i.e., the wrist). Notably, the sensitivity to innocuous and noxious mechanical stimuli were inversely correlated across areas, such that areas with higher tactile sensitivity displayed higher pain thresholds. In addition, the dominant hand was less sensitive than the non-dominant one, and women displayed higher sensitivity than men. Together, this work provides the first detailed spatial characterization of mechanical sensitivity across the human hand and introduces a systematic methodology for its assessment. These findings set the stage for future studies of the neurophysiological mechanisms of touch and pain in the human hand and for clinical research into pathological conditions involving the altered hand sensitivity.

physiology↗

bioRxiv2022

Structural plasticity of axon initial segment in spinal cord neurons underlies inflammatory pain

Activity-dependent structural plasticity of axon initial segment (AIS) regulates neuronal excitability, thus fine-tuning neuronal and overall network output. Here using behavioral, immunohistochemical, electrophysiological and computational approaches, we describe the structural plasticity of AIS in rats superficial spinal cord dorsal horn (SDH) neurons, which underlies inflammatory pain. We show an inflammation-mediated distal shift of the AIS away from the soma in inhibitory but not excitatory SDH neurons, concomitant with the peak of inflammatory pain. This AIS translocation was accompanied by a decrease in excitability of the inhibitory neurons. Following recovery from inflammatory hyperalgesia, the AIS location and neuronal excitability reversed to baseline levels. The computational model of SDH inhibitory neurons predicts that the distal shift of AIS is sufficient to decrease the intrinsic excitability of these neurons. Our results provide evidence of differential inflammation-mediated AIS plasticity, reducing the excitability of inhibitory but not excitatory SDH neurons and contributing to inflammatory hyperalgesia.

neuroscience↗