Currently, Piezo2 is thought to be channel protein underlying the transduction for cutaneous mechanical rapidly adapting responses, because it forms a nonselective cation pore that opens in response to mechanical stimuli. Moreover, the activation and inactivation kinetics of this channel are consistent with its causing the rapidly adapting mechanoactivated current, and it is blocked by agents (gadolinium, ruthenium red) that block these rapidly adapting currents. Furthermore, transfection of ganglion cells with small interfering (si)RNA for Piezo2 blocks the rapid mechanoactivated current in these cells. Lastly, messenger (m)RNA expression of Piezo2 has been shown in dorsal root ganglion cells.
Both low-threshold (light touch) and nociceptive-type ganglion cells have been found to express Piezo2, indicating that it plays a role in both innocuous and painful touch sensation. The Piezo proteins (Piezo1 and Piezo2) are both found in a variety of organs and thus may underlie visceral sensation as well. Piezo2 has been found in the main proprioceptors (muscle spindles and Golgi tendon organs [see ]) and appears to be the main mechanotransducer protein there as well.
The receptor that binds capsaicin (the molecule in chili peppers responsible for their spiciness) has been identified, and either it or one of a family of related proteins has been found to be expressed in populations of dorsal root ganglion cells. These proteins belong to the TRP (transient receptor potential) protein family and are currently the most likely candidates for being the transducers of thermal sensations.
It is important to note that many ion channels (and other proteins, e.g., enzymes) are sensitive to temperature; however, in the case of TRP channels, temperature is acting directly as the gating mechanism. The temperatures at which specific TRP channels are active are indicated by arrows in
Fig. 7.8 (bottom), in which the direction of each •Fig. 7.8 Temperaturedependenceoffiringratesindifferentthermo-sensitiveafferents.BelowthefiringratecurvesareshowntherangesoverwhichthedifferentTRPchannelsareactivated.Thedirectionofincreasingactivationisindicatedbyanarrowineachcase.Notehowinsomecasestherangeoverwhichanafferentisactive(topgraphs)correspondswelltotheactivationrangeofasingleTRPchannel,thussuggestingthattheafferentwouldneedtoexpressonlyasingletypeofchannel.InothercasestheactiverangeoftheafferentsuggeststhatmultipleTRPchannelswouldbeneededtounderliethecompleteresponsivenessoftheafferent.
arrow indicates which temperatures cause greater activation. For comparison,
Fig. 7.8 also plots the firing rates of several thermosensitive fibers as a function of temperature. Note how the response ranges of the afferents largely match up with those of individual heat-sensitive channels. The cold fibers, however, show firing over a wider range than any one TRP channel does. One possible explanation for this discrepancy is that dorsal root ganglion cells may express multiple classes of TRP, which would enable them to respond over a wider range of physiological temperatures.