1. The capsaicin response of TRPV1 is transient, i.e., the current is desensitiz

Question

1. The capsaicin response of TRPV1 is transient, i.e., the current is desensitized after initial activation when the external solution contains calcium ions. In addition, the current cannot be reactivated subsequently for a prolonged duration. Explain possible mechanisms that may cause the phenomena. 2. The topical application of capsaicin has an analgesic effect, meaning that it can render sensory neurons not only irresponsive to subsequent application of capsaicin but also irresponsive to other types of stimuli such as mechanical stimulus. Explain how this might happen. 3. Piezo channels inactivate and can lose inactivation in groups. How do you think the channels might communicate the loss of inactivation? 4. Piezo channels are large. What do you think might be the advantage to being big? 1. The capsaicin response of TRPV1 is transient, i.e., the current is desensitized after initial activation when the external solution contains calcium ions. In addition, the current cannot be reactivated subsequently for a prolonged duration. Explain possible mechanisms that may cause the phenomena. 2. The topical application of capsaicin has an analgesic effect, meaning that it can render sensory neurons not only irresponsive to subsequent application of capsaicin but also irresponsive to other types of stimuli such as mechanical stimulus. Explain how this might happen. 3. Piezo channels inactivate and can lose inactivation in groups. How do you think the channels might communicate the loss of inactivation? 4. Piezo channels are large. What do you think might be the advantage to being big? 2. The topical application of capsaicin has an analgesic effect, meaning that it can render sensory neurons not only irresponsive to subsequent application of capsaicin but also irresponsive to other types of stimuli such as mechanical stimulus. Explain how this might happen. 3. Piezo channels inactivate and can lose inactivation in groups. How do you think the channels might communicate the loss of inactivation? 4. Piezo channels are large. What do you think might be the advantage to being big?

Explanation / Answer

ANS 1) The pharmacological desensitization of receptors is a fundamental mechanism for regulating the hobby of neuronal structures. the trpa1 channel performs a key function inside the processing of noxious information and may undergo functional desensitization through unknown mechanisms. here we display that trpa1 is desensitized through homologous (mustard oil; a trpa1 agonist) and heterologous (capsaicin; a trpv1 agonist) agonists through ca2+-independent and ca2+-dependent pathways, respectively, in sensory neurons. the pharmacological desensitization of trpa1 with the aid of capsaicin and mustard oil is not prompted through activation of protein phosphatase 2b. however, it is regulated with the aid of phosphatidylinositol-four,5-bisphosphate depletion after capsaicin, but now not mustard oil, utility. the usage of a biosensor, we establish that capsaicin, in contrast to mustard oil, consistently activates phospholipase c in sensory neurons. we subsequent display that trpa1 desensitization is regulated by way of trpv1, and it seems that mustard oil-prompted trpa1 internalization is avoided by coexpression with trpv1 in a heterologous expression gadget and in sensory neurons. in conclusion, we endorse novel mechanisms whereby trpa1 interest undergoes pharmacological desensitization via a couple of mobile pathways which can be agonist dependent and modulated through trpv1.

ANS 2) Capsaicin applied to the peripheral nerves provide conduction blockade. In contrast to the analgesic component of conduction anesthesia produced by local anesthetics, vanilloid agonists provide conduction analgesia not associated with suppression of motor or sensory functions not related to pain

ANS 3) Piezo1 is a eukaryotic cation-selective mechanosensitive ion channel. To understand channel function in vivo, we first need to analyze and compare the response in the whole cell and the patch. In patches, Piezo1 inactivates and the current is fit well by a 3-state model with a single pressure-dependent rate. However, repeated stimulation led to an irreversible loss of inactivation. Remarkably, the loss of inactivation did not occur on a channel-by-channel basis but on all channels at the same time. Thus, the channels are in common mechanical domain.

ANS 4) Piezo channels are large because they subsequently are isolated and encoded into a protein of approximately 2,500 amino acids with over 30 predicted trans-membrane regions and with no obvious homology to other channel proteins.1 Heterologous expression of Piezo1 conferred mechanosensitive whole cell currents to cells that did not normally respond and hence, may be the advantage of having big piezo channels

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