DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

368
A Ion channels α 1 subunits for Ca 2+ , Na + channels
I II III IV
outside
membrane
SECTION II
Voltage
sensing
S4 transmembrane
segment
inactivation
region
inside
C
PKA site
NEUROPHARMACOLOGY
N
modulation by PKA, PKC
PKC site
Inactivation trimer
Glycosylation site
Pore region
B
Multi-subunit assembly of Ca 2+ channels
α 2 and δ
γ α 2
α 1
δ
N
N
S
S
α 2
C
β
Cytosolic
N C
γ
β
Ca 2+
C
δ
N
C
C
Structure diversity of K + channels
K + channel
α
Inward
rectifier
K + channel
N
C
β
N
C
N
C
Figure 14 –2. Structural similarities of voltage-dependent Na + , Ca 2+ and K + channels. A. The α subunit in both Ca 2+ and Na + channels
contains four subunits, each with six transmembrane hydrophobic domains. The hydrophobic regions that connect segments five and
six in each domain form the pore of the channel. Segment four in each domain includes the voltage- sensor. See Figure 20–2 for additional
details. (Adapted with permission from Catterall W. From ionic currents to molecular mechanisms: The structure and function
of voltage-gated sodium channels. Neuron, 2000, 26:13–25. Copyright © Elsevier.) B. The Ca 2+ channel also requires several auxiliary
small proteins (α 2
, β, γ, and δ). The α 2
and δ subunits are linked by a disulfide bond. Regulatory subunits also exist for Na + channels.
C.Voltage-sensitive K + channels (K v
) and the rapidly activating K + channel (K A
) share a similar putative hexaspanning structure
similar in overall configuration to one repeat unit within the Na + and Ca 2+ channel structure, while the inwardly rectifying K + channel
protein (K ir
) retains the general configuration of just loops five and six. Regulatory β subunits (cystosolic) can alter K v
channel
functions. Channels of these two overall motifs can form heteromultimers.