Neuromodulation of Heart Functions with Infrared Light – Candidate Targets: TRP Channels

Abstract

Neurostimulation regulates important physiological parameters including blood pressure, heart rate, and respiration. For this reason, neurostimulation has been considered as a therapy in many contexts (e.g., deep brain stimulation, cardiac pacemakers). Our group has discovered that using infra‐red (IR) light can be used to pace the embryonic and adult heart and modulate neuronal activity up and down. Application of a focused IR beam to small areas of the rat nodose ganglion uncovered regional functional specificity. The IR laser beam focused different regions of the ganglion elicited distinct physiological responses in blood pressure and breathing. The mechanism of IR impulse modulation is unknown but hypothesized to work through the creation of temperature gradients. In this study, we report the location of candidate target molecules in ganglia that might be triggered by IR exposure and may be responsible for the modulating effects on neuronal activity. The proposed target molecules are the transient receptor potential (TRP) channels, a calcium channel superfamily whose members are heat‐ and mechano‐sensitive. These channels are divided into several different families and are specialized for sensing different temperature ranges (noxious heat, non‐noxious heat, cold). In this study we focused on an expression of TRPV1, which is considered to be one of the main heat sensitive TRPs and is known to regulate synaptic vesicle recycling. Another important heat sensitive receptor, which is thought to work with TRPV1 is TRMP3. It has properties that make it a more promising target of the therapeutic pain control. Here we report spatial localization and distribution of various TRPs in rat and mouse nodose and superior cervical ganglion studied by immunohistology imaged using epifluorescence and confocal microscopy and in some cases tissue clearing protocols. TRPV1 and TRPM3 are found in a subset of neurons within the ganglia. These are found in clusters and scattered throughout the ganglia. TRPV1 and TRPM3 are both found in the cytoplasm evenly distributed or in some cells in a granular distribution. Both channels are expressed in small or medium size neurons. Some of the others TRPs receptors are found in neurons in rat ganglia, others are predominantly expressed in glial cells. From our preliminary data the TRP channels are present and could play an important role in heat sensing in the ganglia. There heterogeneous distribution within the ganglia could explain the region specific physiological responses. Our goal is to determine the 3‐D spatial localization of these and other IR sensitive channels in the nodose and superior cervical ganglia that modulate the function of many organ systems.Support or Funding InformationNIH grant: 1OT2OD025307‐01, Fulbright Foundation, Operational Programme Research, Development and Education (reg. n. CZ.02.2.69/0.0/0.0/16_027/0008495), Ministry of Education CZ ‐ Progres Q38.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.