Integrin alpha2beta1 affects mechano-transduction in slowly and rapidly adapting cutaneous mechanoreceptors in rat hairy skin.
The role of a transmembrane protein, integrin alpha2beta1, to modulate the neural responses of cutaneous mechanoreceptors to mechanical indentation was examined using an isolated skin-nerve preparation in a rat model. Skin and its intact innervation were harvested from the medial thigh of the hindlimb and placed in a dish containing synthetic interstitial fluid. Using a standard teased nerve preparation, the neural responses of single slowly or rapidly adapting mechanoreceptors (SA or RA, respectively) were identified and the afferents categorized according to standard protocols (i.e. response to constant stimuli). The most sensitive spot of a mechanoreceptor's receptive field was identified and then stimulated using controlled compressive stress (constant or dynamic loads between threshold and saturation load for SAs and RAs, respectively). Loads were applied before, during, and after passive diffusion into the skin of a function-blocking anti-integrin alpha2 monoclonal antibody (FBmAb) or one of two types of control antibodies (immunoglobulin G or a FBmAb conjugated with a secondary antibody). The sensitivities of both SA and RA mechanoreceptors were profoundly reduced in the presence of the FBmAb, while not changing the waveforms of their action potentials or their adaptation properties. Both control antibodies had no significant effect on mechanoreceptors' sensitivities. Following removal of the FBmAb, the effects in some neurons were partially reversible. Taken together, the data from this study support the hypothesis that integrin alpha2beta1 plays a significant role in modulating mechanoreceptive response to compressive indentation.
Khalsa
P S
PS
Department of Biomedical Engineering, State University of New York, HSC T18-031, Stony Brook, NY 11794-8181, USA. partap.khalsa@stonybrook.edu
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Uddin
M Zia
MZ
Hadjiargyrou
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D000222:Adaptation, Physiological / Q000502:physiology; D000465:Algorithms; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D006197:Hair / Q000502:physiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D007700:Kinetics; D008465:Mechanoreceptors / Q000378:metabolism / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000294:innervation; D012879:Skin Physiological Phenomena
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D038982:Integrin alpha2beta1