Abstract:
revealed TRPM2 protein expression in SNc neurons, whereas TRPV4 was detected in astrocytes. The protein expression of TRPM7 and TRPV3 was not tested. Intracellular application of ADPR, an activator of TRPM2 channels, evoked a dose‐dependent inward current and [Ca2+]i rise in SNc neurons. The response was inhibited by non‐selective TRPM2 channel blockers clotrimazole and flufenamic acid. Bath application of H2O2 evoked a complex response that was mediated in part by KATP channels. TRPM2 channels were also activated, as demonstrated by partial inhibition of the response with clotrimazole and N‐(pamylcinnamoyl) anthranilic acid (ACA). The response was also shown to be dependent on [Ca2+]o and resting [Ca2+]i, providing additional evidence for the activation of these channels at the plasma membrane. SNc neurons demonstrated strong sensitivity to temperature changes (24–39 °C): warming induced an increase in firing frequency, [Ca2+]i and an inward whole‐cell current. These responses were comparable to those observed by others with activation of TRPV3 or TRPV4 channels in heterologous expression systems. Although the current response was partially inhibited by ruthenium red, a non‐selective blocker of TRP channels, the lack of selective antagonists hindered identification of the specific channels activated. SNc astrocytes displayed similar temperature sensitivity, but were unresponsive to hypoosmolarity. TRPV4 channels expressed in heterologous systems are typically responsive to changes in both temperature and osmolarity. Data obtained in this study provide novel information on the expression and role of the four TRP channels in the SNc of the rat, and form a basis for further investigations into the role of these channels in the pathophysiological processes leading to PD.
