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
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© 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
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