Pharmacology & Physiology
Research Interests
Research Interests of the Rohacs lab: Transient Receptor Potential (TRP) channels
TRP channels
TRP channels have received a lot of attention recently, because of their involvement in a variety of important biological processes. Their function is remarkably diverse, they are involved in temperature sensation, mechanosensation, vision, taste, Ca 2+ and Mg 2+ transport across epithelial cells, apoptosis and Ca 2+ signaling by hormones and neurotransmitters. TRPC (Classical) channels are activated upon the activation of Phospholipase C (PLC). Despite intensive research the exact mechanism by which they turn on upon PLC activation is still not completely clear. Members 1-4 of the TRPV (Vanilloid) family are activated by warmth, and TRPV5 and TRPV6 function as Ca 2+ transporters in the intestines and kidneys. The TRPM (Melastatin) family is the most diverse functionally, they are involved in processes as diverse as cold sensation, Mg 2+ transport and redox stress sensation.
Temperature and pain sensation
Among TRP channels, our laboratory mainly focuses on the heat and capsaicin activated TRPV1 and the cold and menthol sensitive TRPM8 channels. Both these channels are expressed in sensory neurons: dorsal root ganglia (DRG) and trigeminal ganglia (TG). TRPV1 is activated by hot temperatures, capsaicin and a number of other pain producing stimuli, such as a drop in pH. Capsaicin, has been used for a long time as a topical analgesic, after an initial burning sensation, it provides pain relief, because TRPV1 becomes desensitized not only to capsaicin, but also to other pain producing stimuli. We are currently studying the mechanism of this desensitization. TRPM8 on the other hand is activated by cold temperatures and menthol. Menthol is also used a topical analgesic, its cooling effect however is transient, again, due to desensitization. Our data show that the desensitization of both channels is caused by activation of PLC and the ensuing depletion of PIP2 (see later).
Phosphoinositide signaling and TRP channels
Phosphatidylinositol 4,5-bisphosphate (PIP2) is a minor, but biologically important component of the plasma membrane. PIP2 is likely to be a common regulator of TRP channels. Our laboratory focuses on understanding how phosphoinositides regulate TRP channels, and what the physiological importance of this regulation is. We have found that Ca 2+ influx through TRPM8, TRPV1 and TRPV6 activates a Ca 2+ sensitive PLC isoform, and the resulting depletion of PIP2 leads to desensitization/inactivation of these channels. We are using various electrophysiological and molecular techniques to study the regulation of TRP channels by PIP2 .
