MUTAGENESIS AND TEMPERATURE-SENSITIVE LITTLE MACHINES

Abstract

In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.In mammals a class of ion channels able to sense a wide range of temperatures (0-60 °C) has evolved. These molecular thermodynamic machines called thermo Transient Receptor Potential (thermoTRP) are spread through the different TRP channel subfamilies having members inside the TRPM (melastatin) subfamily, where TRPM2, TRPM3, TRPM4 and TRPM5 are heat-activated, whereas TRPM8 is activated by cold. The TRPV (vanilloid) subfamily contains four thermoTRP channels (TRPV1, TRPV2, TRPV3 and TRPV4), which are all activated by heat; and TRPA1 (ankyrin) channel which is activated by noxious cold (reviewed in [28, 107], Figure 1). More recently, a member of TRPC (canonical) subfamily, TRPC5, was identified as a cold receptor in the temperature range 37-25 °C [1].

Located in cutaneous nerve endings of thermoreceptors and nociceptors, and because extreme temperatures produce discomfort and pain, thermoTRP channels are involved in nociception and can be activated by a long list of other noxious stimuli such as low pH and irritant chemicals [2].

What characterizes these channels is their exquisite temperature sensitivity. Thermodynamic analyses reveal that thermoTRP channels undergo large enthalpy changes (?H) that account for their high temperature sensitivity [3-8]. For example, the enthalpy change between close and open in TRPV1 and TRPM8 involves ?Hs of ~100 kcal/mol and ~-60 kcal/mol, respectively [3, 5]. It is obvious that in order to make the closed-open reaction reversible these enthalpy changes must be accompanied by large entropy (?S) changes. These activation enthalpies are 3-5 times the enthalpy change for voltage- or ligand-dependent channel gating (?H ~20 kcal/mol; [108]). Actually, Yao et al. [7] pointed out that in the case of TRPV1, the ?H involved in the closed-open transition is equivalent to an electrical energy moving 71 unit charges across 60 mV.