生物物理学 II Handout No. 7①②Figure 13-3 A G protein-coupled
receptor contains seven membranespanning domains. The b2-adrenergic
receptor shown here is structurally similar toother G protein-coupled metabotropic
receptors, including the b1-adrenergic andmuscarinic ACh receptors and rhodopsin.
An important functional feature is that thebinding site for the neurotransmitter lies in aclett in the receptor that is embedded in thelipid bilayer accessible from the extracellularsurface of the cell. The amino acid residue
aspartic acid-113 (Asp113, in dark blue)
participates in binding. The part of thereceptor indicated in brown is the part withwhich G protein associates. The two serine
residues (yellow) are sites for phosphorylation, which is involved in inactivating thereceptor. (Adapted from Frielle et al. 1989.)③

Figure 63-9 Long-term potentiation (LTP) in the Schaffer collateralpathway to the CA7 region of the hippocampus.
A. Experimental setup for studying LTP in the CA7 region of thehippocampus. The Schaffer collateral pathway is stimulated electricallyand the response of the population of pyramidal neurons is recorded.
B. Comparison of early and late LTP in a cell in the CA1 region of thehippocampus. The graph is a plot of the slope (rate of rise) of theexcitatory postsynaptic potentials (EPSP) in the cell as a function of time.
The slope is a measure of synaptic efficacy. Excitatory postsynaptic
potentials were recorded from outside the cell. A test stimulus was given
every 60 s to the Schaffer collaterals. To elicit early LTP a single train ofstimuli is given for 1 s at 100 Hz. To elicit the late phase of LTP four
trains are given separated by 10 min. The resulting early LTP lasts 2-3hours, whereas the late LTP lasts 24 or more hours.

Figure 63-10 A model for the induction of the early phaseof long-term poten- tiation. According to this model NMDA andnon-NMDA receptor-channels are located near each other in dendriticspines.
A. During normal, low-frequency synaptic trans- mission glutamate (Glu)is released from the presynaptic terminal and acts on both the NMDA andnon-NMDA receptors. The non-NMDA re- ceptors here are the AMPA
type. Na+ and K+ flow through the non-NMDA channels but not throughthe NMDA channels, owing to Mg 2+ blockage of this channel at theresting level of membrane potential.
B. When the postsynaptic membrane is depo- larized by the actions of
the non-NMDA receptor- channels, as occurs during a high- frequency
tetanus that induces LTP, the depolarization relieves the Mg 2+ blockageof the NMDA channel. This allows Ca 2+ to flow through the NMDAchannel. The resulting rise in Ca 2+ in the dendritic spine triggers
calcium-dependent kinases (Ca2+/calmodulin kinase and protein kinaseC) and the tyrosine kinase Fyn that together induce LTP TheCa2+/calmodulin kinase phosphorylates non-NMDA receptor-channels
and increases their sensitivity to glumate thereby also activating someotherwise silent receptor channels. These changes give rise to a
post-synaptic contribution for the maintenance of LTP. In addition, once
LTP is induced, the postsynaptic cell is thought to release (in ways thatare still not understood) a set of retrograde messengers, one of which isthought to be nitric oxide, that act on protein kinases in the presynapticterminal to initiate an enhancement of transmitter release that contributes
to LTP.