Introduction and Methodology
Pp. 3-61 (59)
Boris V. Krylov, Ilia V. Rogachevskii, Tatiana N. Shelykh and Vera B. Plakhova
Discovery of NaV1.8 channels has opened a new perspective to study the
mechanisms of nociception. A remarkable feature of these channels is their ability to be
modulated by binding of various endogenous and exogenous agents to membrane
receptors coupled to NaV1.8 channels. The behavior of their activation gating system
was patch-clamp recorded and analyzed by the Almers’ limiting slope method. It was
established that opioid-like membrane receptors could control the functioning of
NaV1.8 channels. A novel role in this mechanism is played by Na+,K+-ATPase, which
serves as the signal transducer instead of G proteins. Switching on the opioid-like
receptors one can selectively decrease the effective charge of NaV1.8 channel activation
gating device. As a result, only the high-frequency component of nociceptive
membrane impulse firing is inhibited. This is the component that transfers nociceptive
information to CNS.
The three units involved in the described membrane signaling cascade (opioid-like
receptor → Na+,K+-ATPase → NaV1.8 channel) are potential targets for novel
analgesics. Investigation of this mechanism of nociceptive signal modulation is of
major importance not only for fundamental physiology but also for clinical medicine.
Impulse firing, Limiting slope procedure, NaV1.8 channels, Na+, K+-
ATPase, Nociception, Opioid-like receptor, Patch-clamp method.
I.P. Pavlov Institute of Physiology Russian Academy of Sciences St. Petersburg, Russia.