Biology subjects

Kulkarni, Y.

Publications and source records attributed to Kulkarni, Y..

3 recordsLinked to original sources

bioRxiv2026

Voltage-Gated Sodium Channel Modulation Differentially Alters ON and OFF Bipolar Cell Contributions to the Rat ERG

AimThe ERG b-wave is primarily attributed to ON bipolar cell activity, while the contribution of the OFF pathway and the differential role of voltage-gated sodium (NaV) channels in these pathways remain unclear. This study investigated whether pharmacological modulation of NaV channels differentially alters ON and OFF cone bipolar cell responses and ERG b-wave amplitudes. MethodsDark- and light-adapted ERGs were recorded from rats across stimulus intensities spanning rod, mixed rod-cone, and cone pathways (1-1000 lux). ON and OFF cone bipolar cell pathways were pharmacologically isolated using intravitreal cis-PDA. NaV channel activity was modulated via intravitreal administration of lidocaine and lamotrigine (blockers) and veratridine (agonist). Changes in b-wave amplitudes were analysed to assess pathway-specific effects. ResultsBoth lidocaine and lamotrigine significantly globally reduced ERG b-wave across all stimulus intensities, confirming a role for NaV channels in bipolar cell signalling. Pathway isolation revealed differential effects: lidocaine predominantly suppressed ON pathway, whereas lamotrigine preferentially reduced OFF pathway responses. In contrast, veratridine enhanced both ON and OFF pathway activity. These findings indicate that NaV channel activity in ON and OFF cone bipolar cells can be independently and differentially modulated. ConclusionThe ERG b-wave reflects integrated contributions from both ON and OFF cone bipolar cells. Differential NaV channel modulation alters these pathways distinctly, highlighting sodium channel-mediated mechanisms as potential targets for physiologically relevant retinal stimulation strategies in degenerative retinal conditions.

pharmacology and toxicology↗

bioRxiv2025

Collective Response of ON and OFF Bipolar Cells to Light Contributes to Improved Visual Acuity

In the visual signal relay, retinal bipolar cells transduce neurotransmitter signals from photoreceptor cells into electrical signals for onward transmission to the brain. The electrical activity of bipolar cells is reflected in the b-wave of the electroretinogram which is majorly contributed by ON bipolar cells leading to the currently accepted belief that light-induced signals travel through these cells only. Here, we probe the role of ON and OFF pathways to generate visual percept under the hypothesis that the ON Bipolar Cell fine image (central illumination) is superimposed onto a coarser image formed due to OFF Bipolar Cell (surround illumination). This improves image sharpness through edge detection by unsharp masking, thereby contributing to improved visual acuity. This new finding could be useful in stimulating the retina through sub-retinal implants to restore vision.

neuroscience↗

bioRxiv2023

A sensor complements the steric gate when DNA polymerase ϵ discriminates ribonucleotides.

The cellular imbalance between high concentrations of ribonucleotides (NTPs) and low concentrations of deoxyribonucleotides (dNTPs), is challenging for DNA polymerases when building DNA from dNTPs. It is currently believed that DNA polymerases discriminate against NTPs through a steric gate model involving a clash between a tyrosine and the 2-hydroxyl of the ribonucleotide in the polymerase active site in B-family DNA polymerases. With the help of crystal structures of a B-family polymerase with a UTP or CTP in the active site, molecular dynamics simulations, biochemical assays and yeast genetics, we have identified a mechanism by which the finger domain of the polymerase sense NTPs in the polymerase active site. In contrast to the previously proposed polar filter, our experiments suggest that the amino acid residue in the finger domain senses ribonucleotides by steric hindrance. Furthermore, our results demonstrate that the steric gate in the palm domain and the sensor in the finger domain are both important when discriminating NTPs. Structural comparisons reveal that the sensor residue is conserved among B-family polymerases and we hypothesize that a sensor in the finger domain should be considered in all types of DNA polymerases.

biochemistry↗