生物物理学 II Handout No. 6①FIGURE 11.25 Coincident In- creases in Membrane Capaci- tance and Release of Catecholamines from chromaffin cells. (A) A carbon fiber electrode inside the patch pipette measures catecholamine
release by amperometry, while at the same time the electrode is used to measure capaci- tance within the patch.
(B) Simultaneous recording of catecholamine release (top trace) and capacitance (bottom trace). All exocytic
events detected by catechol- amine release coincide with increases in capacitance. (C) The sixth and seventh
exocytic events in part B, displayed on an expanded scale. The sixth exocytic event coincides with a transient,
flickering increase in capacitance that lasts about 5 s. The seventh exocytic event coincides with an abrupt andlong-lasting increase in capacitance. (D) Transient increases in capacitance may correspond to exo- cytosis
through a temporary fusion pore that rapidly closes, allowing the vesicle to pinch back off into the cytoplasm
without ever becoming incorporated into the plasma membrane. Under such cir- cumstances small molecules
may be released while larger proteins are retained in the vesicle. (After Albinos et al., 1997.)②
Figure 12-10 The three familiesof ligand-gated channels.
A. The ATP-gated channels possess twomembrane-spanning domains (M1 andM2) and a large extracellular loop. Their
subunit stoichiometry is not known.
B1. The nicotinic ACh, GABAA, and glycine receptor-channels are all pentamers
composed of several types of related
subunits (B2). As shown here (B1), each
subunit has four transmembrane domains (M1-M4). The M2 domain lines thechannel pore.
C. The glutamate receptor-channels arethought to be tetramers composed of two
different types of closely related subunits (here denoted 1 and 2) (C2). The subunits
have three transmembrane domains (M1, M3, and M4) and one region (M2) that forms
a loop that dips into the membrane. The M2 loop lines the channel pore. The
glutamate binding site is formed by residues in the extracellular amino terminus
preceding the M1 domain and in the extracellular loop connecting the M3 and M4
domains. The three-dimensional structure of the extracellular glutamate binding
domain of a subunit of the AMPA-type of glutamate receptor (GluR2) has been solved
by X-ray crystallography. The binding site is a bilobed "clamshell" structure (C 3 )formed by the extracellular NH2 terminal portion of a subunit (domain 1, green) andthe extracellular loop connecting the M3 and M4 segments (domain 2, purple). Herethe subunit has bound a molecule of kainate (which is a weak agonist at AMPA
receptors). (From Armstrong et al. 1998.)③Figure 13-1 All known neurotransmitter
receptors can be divided into two groups
according to the way in which receptor and effector
functions are coupled.
A. Ionotropic receptors directly gate ion channels as
part of a single macromolecule that also forms the ionchannel. The receptor, located on the extracellular side,and the ion channel pore, embedded in the cell
membrane, are formed within the same protein.
B. Receptors that indirectly gate ion channels fall into
two families. 1. Metabotropic G protein-coupled
receptors activate ion channels and other substrates
indirectly by activating a GTP-binding protein that often
engages a second-messenger cascade. 2. Receptor
tyrosine kinases modulate the activity of ion channels
indirectly through a cascade of protein phosphorylation
reactions, beginning with autophosphorylation of thekinase itself on tyrosine residues.