Bear et al. 2001, Neuroscience, 2nd ed. The Impact of Neurotransmitters Metabotropic Receptors.
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Transcript of Bear et al. 2001, Neuroscience, 2nd ed. The Impact of Neurotransmitters Metabotropic Receptors.
Bear et al. 2001, Neuroscience, 2nd ed.
The Impact of Neurotransmitters
Metabotropic Receptors.
Bear et al. 2001, Neuroscience, 2nd ed.
The Impact of Neurotransmitters
Metabotropic Receptors can regulate ion-channels or enzymes.
α βγ
α βγ
Bear et al. 2001, Neuroscience, 2nd ed.
The Impact of Neurotransmitters
Ion-channel modulation via metabotropic receptor binding.
α βγ
G-protein modulation of channels can be either “direct” or “indirect”
Adrenergic depression of ICa is clearly voltage dependent
Bean, BP, Nature (1989) 340:153-156
Opioid depression of ICa is also clearly voltage dependent
Bean, BP, Nature (1989) 340:153-156
“Fast and voltage-dependent depression of ICa can be described by the “willing/reluctant” model
Bean, BP, Nature (1989) 340:153-156
Many neurotransmitters depress ICa via a fast, voltage-dependent mechanism
The “willing/reluctant” mechanism of Ca2+ channel modulationThe effector subunit of the G/ heterotrimer is the dimer
Regulation of Ca2+ channels directly controls neurotransmitter release
Gq
Stimulation of Gq/11-coupled receptors results in PLCactivation, PIP2 hydrolysis and release of several second messengers
GP
CR
ADAG
ER
IP3
PA AA
PKC
Inhibition of channels isolated in cell-attached patches by bath-applied agonist implies a “diffusible messenger”
Zhang et al., Neuron. 2003. 37:963-75
modified scheme of Soejima and Noma, 1984.
Acetylcholine(oxotremorine) Ca2+
Ca2+ channels are sensitive to PIP2 in the membrane, and Gq/11-mediated muscarinic suppression of ICa involves depletion of PIP2.
PLC-PH translocation
Kir2.1 Kv7.2
K452
R459
R461R463
R467R189
K219
R218
R228
A B
β1
β2β3
β4
β6
β7β5
Kir channels and Kv7 channels share a similar PIP2-binding motif
Structural homology model of PIP2-binding loop of Kv7.2, docked with a PIP2 analog
Gq
Stimulation of Gq/11-coupled M1 receptors inhibits M-type K+ and N-type Ca2+ channels via PIP2 depletion
M1R
A
IP3
XM/C
a2+
Ca2+ channels are heavily regulated
Calmodulin mediates both Ca2+-dependent inactivation and facilitation
Downloaded from: StudentConsult (on 17 December 2004 11:22 PM)
© 2004 Elsevier
Synaptic inputs can add together
Figure 4-10 A, Spatial and temporal summation at a postsynaptic neuron with two synaptic inputs (1 and 2). B, Spatial summation. The postsynaptic potentials in response to single action potentials (aps) in inputs 1 and 2 occur separately and simultaneously. C, Temporal summation. The postsynaptic response to two impulses in
rapid succession in the same input.
Downloaded from: StudentConsult (on 17 December 2004 11:22 PM)
© 2004 Elsevier
Short-term facilitation occurs upon rapidly repeated stimulation of synapses
Long-Term Potentiation May Underlie Learning and Memory
Malenka, R.C. and Nicoll, R.A., Science, Vol 285, Issue 5435, 1870-1874
Bursting controlled by Ca2+-activated K+ channels
0 40 80Time (s)
EM
light=[Ca]
50 m
V
Recording from a secretory neuron of Aplysia shows Ca2+ entry during burst, triggering repolarization and termination of burst. (Gorman & Thomas, 1978)
0.
1% C
a
5 s
slow after- hyperpolarizations
Electrical activity of beta cell in islet: high glucose
Depolarize membrane V-gated Ca2+ channels open
Mem
bran
e po
tent
ial
10 m
V
10 secTime
Mouse pancreatic islet in 11 mM glucose (200 mg/dl)
beta cell
Ca2+ enters exocytosis of insulin granules
(Cook, 1980)
Neuroendocrine cells secrete hormones like neurons secrete neurotransmitters
Regulation of secretion in electrically excitable cells:Depolarization Ca2+ entry through Ca2+ channels
Pituitary somatotropeGHRH Growth hormone
Synapse (presynaptic)Action potential Neurotransmitter
Chromaffin cellACh Adrenaline
Pancreatic cellGlucose Insulin
SpermEgg jelly Acrosome reaction
Secretion of
Membrane potentials
+
+
Roles of ion channels
Electrical signals Ca2+
signalsIon
transport
Cell Membrane
Out
In
Ions
Three roles channels