Effective suppression of I h and I Na caused by capsazepine, known to be a blocker of TRPV1 receptor

• Published in: Brain research 2024-09, Vol.1839, p.149008
• Main Authors: Wong, Siew-Lee, Shih, Chia-Lung, Cho, Hsin-Yen, Wu, Sheng-Nan
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Animals; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Cell Line, Tumor; Membrane Potentials - drug effects; Neurons - drug effects; Neurons - metabolism; Patch-Clamp Techniques; Rats; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - drug effects; TRPV Cation Channels - metabolism
• ISSN: 1872-6240
• DOI: 10.1016/j.brainres.2024.149008

A synthetic inhibitor of capsaicin-induced TRPV1 channel activation is called capsazepine (CPZ). In this study, we aimed to explore the effects of CPZ on hyperpolarization-activated cationic current (I ) and voltage-gated Na + current (I ) in pituitary tumor (GH ) cells. Through patch-clamp recordings, we found that CPZ concentration-dependently inhibited I amplitude and slowed its activation time course. The IC and K values were 3.1 and 3.16 μM, respectively. CPZ also shifted the steady-state activation curve of I towards a more hyperpolarized potential. However, there was no change in the gating charge of the curve. A modified Markovian model predicted the CPZ-induced decrease in the voltage-dependent hysteresis of I . CPZ suppressed I in GH cells, without altering its activation or inactivation time course. Additionally, exposure to CPZ reduced spontaneous firing. These findings suggest that CPZ's inhibitory effects on I and I are direct and not dependent on vanilloid receptor binding. This could provide light on an unidentified ionic mechanism influencing the membrane excitability of neurons and endocrine or neuroendocrine cells in vivo.