TRPV1 regulates activation and modulation of TRPA1 by Ca 2+

The transient receptor potential A1 (TRPA1) channel contributes to nociceptive signaling in certain pain models. It has been suggested that Ca 2+ , which activates and modulates TRPA1, could play a critical regulatory role in this process. Since TRPA1 and TRPV1 channels are co-expressed and interact in neurons, we investigated whether activation and modulation of TRPA1 by Ca 2+ is regulated by TRPV1. Cell-attached recordings showed that TRPA1 is activated by extracellular Ca 2+ ([Ca 2+ ] e ) in concentration-response fashion. This activation, especially by 2mM [Ca 2+ ] e was substantially suppressed by co-expression with TRPV1. Inside-out recordings demonstrated that intracellular Ca 2+ ([Ca 2+ ] i )-triggered activation of TRPA1 was attenuated by the presence of TRPV1 only at 2 mM [Ca 2+ ] e , but not in Ca 2+ -free conditions. Further, depletion of internal Ca 2+ stores by thapsigargin generated TRPA1-mediated currents, which is affected by TRPV1 in both Chinee hamster ovary cells and sensory neurons. , we next examined the Ca 2+ ] e ; the influence of [Ca 2+ ] e on the voltage-dependency of I MO , and open probability of single-channel I MO . In summary, activation of TRPA1 by [Ca 2+ ] e and [Ca 2+ ] i is controlled by the TRPV1 channel, and characteristics of I MO depend on Ca 2+ permeability of the TRPV1 channel.

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