The Role of Allosteric Coupling on Thermal Activation of Thermo-TRP Channels

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• 作者：André ; s Jara-Oseguera ; Leó ; n D. Islas ; ^{islas@liceaga.facmed.unam.mx}
• 刊名：Biophysical Journal
• 出版年：2013
• 出版时间：21 May, 2013
• 年：2013
• 卷：104
• 期：10
• 页码：2160-2169
• 全文大小：1555 K

文摘

Thermo-transient receptor potential channels display outstanding temperature sensitivity and can be directly gated by low or high temperature, giving rise to cold- and heat-activated currents. These constitute the molecular basis for the detection of changes in ambient temperature by sensory neurons in animals. The mechanism that underlies the temperature sensitivity in thermo-transient receptor potential channels remains unknown, but has been associated with large changes in standard-state enthalpy (¦¤H^o) and entropy (¦¤S^o) upon channel gating. The magnitude, sign, and temperature dependence of ¦¤H^o and ¦¤S^o, the last given by an associated change in heat capacity (¦¤C_p), can determine a channel¡¯s temperature sensitivity and whether it is activated by cooling, heating, or both, if ¦¤C_p makes an important contribution. We show that in the presence of allosteric gating, other parameters, besides ¦¤H^o and ¦¤S^o, including the gating equilibrium constant, the strength- and temperature dependence of the coupling between gating and the temperature-sensitive transitions, as well as the ¦¤H^o/¦¤S^o ratio associated with them, can also determine a channel¡¯s temperature-dependent activity, and even give rise to channels that respond to both cooling and heating in a ¦¤C_p-independent manner.