Lecture 3A and 3B Flashcards
To be able to describe and differentiate between cold and warm temperature sensitive neurons.
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To understand and describe static and dynamic responses of cold and warm temperature sensitive neurons.
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To explain how afferent inputs represented by skin and core temperature participate in the control of human thermoregulatory responses.
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To name and describe 9 membrane channels of interest from the family of Transient Receptor Potential (TRP) membrane channels and how each channel’s conductance changes as a function of it’s temperature.
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To name the chemical agonists for each of these 9 channels interest in the family of Transient Receptor Potential (TRP) membrane channels.
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To understand & describe the mechanisms of how these TRP channels are thought to participate in thermosensation and thermoregulation as well as which TRP channels are active over which range of temperatures.
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What is static response of a temperature sensitive neuron
for a given level of temp there is a given level of firing of the temp sensitive neuron
What is dynamic response of a temperature sensitive neuron
for changing levels of temp, there is an increased level of firing relative to the static firing rate at the temp same level
What is the overshoot seen in temperature sensitive neurons
A dynamic response
The hypothalamus is “integrative center” that gives ____ control of body temp
proportional
Describe the preoptic anterior hypothalamus
- has neurons that INC firing with INC temp
- Stimulates HEAT LOSS responses -> This output is INHIBITED by COLD input from the skin
Describe the dorsomedial posterior hypothalamus
has neurons that INC firing with DEC temp. This output is INHIBITED by WARM input from the skin
As the skin gets cooler the point of onset of sweating is ____
delayed
As core temp increases the onset of shivering is _____
delayed
Certain ion channels of the transient receptor potential (TRP) family can be activated by increases or decreases in _____
temperature
What kind of receptor is TRPM8
cold receptor
What kind of receptor is TRPA1
noxious cold
What kind of receptor is TRPV3 and TRPV4
warm receptor channels triggered by innocuous warm temps
What kind of receptor is TRPV1
sensitive for noxious heat but less support that is involved in thermoregulation
TRPV1, TRPV3, TRPV4, and TRPM8 are ion channels each involved in _____ and possibly
______
- thermosensation
2. thermoregulation
Describe TRPM8 channel (cold or warm receptor, how activated, what range activated, what plant derivative is it activated by)
- potential cold receptor
- activated by either MENTHOL or cool temps
- apparent threshold for TRPM8 activation by cold is 25 °C
- TRM8 expression is confined largely to a subpopulation of small-diameter peripheral sensory neurons that under normal conditions are distinct from those that express TRPV1
Describe how TRPM8 involves a negative feedback Loop for Behavioural Temp Regulation
- If Tskin is < 28.4°C, delta T is neg, then thermoregulatory responses to warm the skin e.g. Brown Adipose Tissue (BAT) - Movement of rodents along floor, heated with a gradient from cool to warm, is the behavioral response
- Cooling-sensitive TRPM8 is directional comparator of skin temps inducing output (y) when DeltaT is neg. If neg DeltaT-dependent output (y) induces thermaregulatory responses to warm skin recursively, neg feedback loops having 28.4°C as set-point temp are formed and TRPM8 fxns as thermostat for minimizing DeltaT against cooling. In behavioural regulation, when room is cooled, TRPM8 induces behaviour to move heated floor to warm the sole skin, which effectively maintains temp of sole skin against cooling. In autonomic regulation, when room is cooled, TRPM8 induces small rise in core temp, but skin temp is severely dec, as if regulation of skin temp not fxning.
Describe TRPV3 (cold or warm receptor, how activated, what range activated, what plant derivative is it activated by)
TRPV3:
- warm receptor
- activated by warm temps btwn 34 and 39°C.
- repetitive stimulation of TRPV3 with heat results in a current response of gradually increasing amplitude
- activated by CAMPHOR, irritant extracts from OREGANO and CLOVES
- expressed within keratinocytes, the stratified epithelial cells that are the major constituents of skin epidermis -> suggests some aspects of heat transduction may not be confined to cutaneous sensory neurons
Describe TRPV4 (cold or warm receptor, how activated, what range activated, what plant derivative is it activated by)
TRPV4:
- warm receptor
- activated by warm temperatures btwn ~25°C to 34°C
- PLANT DERIVATIVE UNKNOWN
- expressed within keratinocytes, the stratified epithelial cells that are the major constituents of skin epidermis -> suggests some aspects of heat transduction may not be confined to cutaneous sensory neurons
Describe TRPV1 (temp range, plant derivative activated by, what blocks it)
- might act physiologically as a transducer of noxious heat, highest conductance at ~ 40-42°C; suggests not involved in temp reg.
- a detector of CAPSAICIN and ARACHIDONIC ACID metabolites
- Ruthenium red (RR) inhibits heat-evoked responses in expressing cells (blocks channel)
4 mechanisms how TRPV1 can be activated
Mechanism 1: TRPV1 activation at the peripheral terminals of cutaneous or visceral warm fibers, whose cell bodies are in DRG, leads to stimulation of neurons w/in the most superficial layer of the SC dorsal horn. These neurons decussate, then ascend w/in spinothalamic tract, and send collateral branches to parabrachial nucleus in pons. Pontine projections to the PO/AH then activate WARM SENSITIVE neurons and/or INHIBIT COLD SENSITIVE neurons
Mechanism 2 and 3: activation of TRPV1 on presynaptic terminals (from the pons or elsewhere) impinging on the PO/AH results in increased excitatory NT release onto warm sensitive neurons (2) or increased inhibitory NT release onto cold sensitive neurons (3)
Mechanism 4: Activation of TRPV1 intrinsic to warm sensitive neurons results in their direct activation
Describe TRPA1 (cold or warm receptor, temp range, plant derivative its activated by). How did mice lacking TRPA1 differ?
- TRPA1 appears to be highly CO-EXPRESSED with TRPV1 in a subset of small- to medium-diameter peripheral sensory neurons
- TRPA1 may act as a SENSOR of PAINFULLY COLD TEMPS… activated by temperatures <18°C.
- ISOTHIOCYANATES (e.g. mustard oil, wasabi, and garlic), as well as other irritant chemicals such as ACROLEIN, can activate this channel
- mice LACKING TRPA1 shown to exhibit BLUNTED behavioral responses to a cold metal surface or to acetone-mediated cooling of the hind paw skin
How is TRPM subfamily TRPM4, TRPM5, TRPM2 activated? What range of degrees?
- by warming
- > 15°C for TRPM4 and TRPM5
- > 35°C for TRPM2.
Where are TRPM channels expressed? Importance?
- none of these channels are expressed in peripheral somatosensory neurons or in skin keratinoctyes,
- suggests they are not involved in temp sensation in skin.
- TRPM5 is expressed in epithelial taste cells in the tongue
- TRPM5 is required for the ability of warm temps to enhance sweet-tastant evoked firing of gustatory neurons in mice
Discuss roles of TRPV1, TRPV3/V4, TRPM8 n thermosensation
Top: sensation of burning pain can b evoked by activation TRPV1 in nociceptive neurons in skin. Many TRPV1-expressing neurons also express TRPA1 which has been proposed to participate in the transduction of painfully cold temps.
Middle: warm temps apparently activate TRPV3, TRPV4, expressed prominently in epidermal keratinocytes.
Bottom: modest skin cooling most likely activates TRPM8, expressed in distinct subset of sensory neurons
To describe the neural pathways of eccrine sweating and cutaneous blood flow responses.
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To understand and describe how plethysmography, iontophoresis and changes in skin resistance are employed to study human heat loss responses.
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To describe the different stages of cutaneous vasodilatation and the underlying physiological control mechanisms of this heat loss response.
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To understand and describe the types of sweating and the physiological control of eccrine sweating response.
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