Background & Aims
The sense of touch is critical for daily tasks including tactile discrimination, social interaction, and environmental exploration. Previous studies have shown that Merkel cell-neurite complexes (MNCs), a main type of tactile end organ, play a central role in the sense of touch. MNCs are located in touch sensitive spots throughout the body especially at human fingertips and whisker hair follicles of non-primate mammals. A MNC consists of a Merkel cell and an A?-afferent ending (Merkel ending) to form a synapse-like structure. We and others have previous shown that the Piezo2 channel in Merkel cells is the sensor of touch. We have further shown that tactile stimuli activate Piezo2 channels in Merkel cells to result in Ca2+-action potentials, which leads to A?-afferent impulses and behavioral tactile responses. However, the mechanism by which tactile-induced excitatory signals on Merkel cells are transmitted to Merkel endings remains elusive and is the focus of this study.
Methods
Ex vivo preparations of whisker hair follicles were obtained from rats and mice and used in the present study. The pressure-patch-clamp recordings were applied at the heminodes and the first nodes of A?-afferent endings that innervated Merkel cells in rodent whisker hair follicles to record excitatory postsynaptic currents (EPSCs), excitatory postsynaptic potentials (EPSPs), and action potentials that were evoked by tactile stimulation to whisker hair follicles. Synaptic physiology, pharmacology, immunohistochemistry, and mousse genetics (knockout of acid-sensing ion channel type 3, or ASIC3) were used in the present study to investigate the ion channels and the transmitters that mediated the mechanically evoked EPSCs, EPSPs, and action potential impulses in the MNCs in whisker hair follicles.
Results
We applied pressure-patch-clamp recordings to the heminode or the 1st node of MNCs in the whisker hair follicles of rats and mice, and found that mechanical stimulation triggered fast excitatory synaptic transmission at the MNCs. We found that the reversal potentials of the EPSCs were over 50 mV, and the ion channels for EPSCs were Na+-selective. Furthermore, the EPSCs were inhibited by the ASIC blocker amiloride and diminazene, but not affected by the adrenergic ?2 receptor antagonist ICI118551 and 5-HT3 receptor blocker VUF10166. These results suggested that the fast excitatory synaptic transmission at MNCs was mediated by ASICs. We showed that ASIC channels were localized at the neurites of MNCs and could be directly activated by protons to elicit excitatory inward currents. We demonstrated that mechanically evoked and ASIC-mediated fast excitatory synaptic transmission at MNCs drove SA1 impulses at A?-afferent terminals. We further showed that mechanically evoked fast excitatory synaptic transmission at MNCs was associated with action potential firing on Merkel cells and mediated by protons. Finally, genetic deletion of ASIC3 channels impaired fast excitatory synaptic transmission at MNCs and diminished SA1 impulses.
Conclusions
Following the initial mechanical transduction via Piezo2, the tactile-induced excitatory signals on Merkel cells are conveyed to A?-afferent endings of MNCs through fast excitatory synaptic transmission. This synaptic transmission was mediated by ASIC channels expressed on A?-afferent endings of MNCs, and the transmitter for the synaptic transmission at MNCs was proton. It is concluded that ASICs are required for tactile encoding at MNCs to enable the sense of touch in mammals.
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Presenting Author
Jianguo Gu
Poster Authors
Topics
- Mechanisms: Biological-Systems (Physiology/Anatomy)