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

Table 14–1
Subtypes of Ca 2+ Channel a
Ca 2+ UNOFFICIAL Ca 2+ CURRENT PRIMARY
CHANNEL NAME TYPE LOCATIONS ANTAGONISTS FUNCTION
Ca v
1.1 BK channel L Skeletal muscle DHP, PAA, BZP EC coupling
Ca v
1.2 L Cardiac muscle DHP, PAA, BZP EC coupling
Endocrine cells
Ca 2+ homeostasis
Neurons
Regulation of transcription
Ca v
1.3 L Endocrine cells DHP, PAA, BZP Hormone secretion
Neurons
Regulation of transcription
Ca v
1.4 L Retina DHP, PAA, BZP Tonic neurotransmitter release
Ca v
2.1 SK1 P/Q Nerve terminals ω-Agatoxin IVA Neurotransmitter release
Dendrites
Dendrite Ca 2+ transients
Ca v
2.2 SK2 N Nerve terminals ω-CTX-GVIA Neurotransmitter release
Dendrites Riluzole Dendrite Ca 2+ transients
Ca v
2.3 SK3 R Cell bodies SNX-482 Ca 2+ -dependent action potentials
Dendrites
Dendritic Ca 2+ transients
Nerve Terminals
Ca v
3.1 Gardos channel T Cardiac muscle Mibefradil Repetitive firing of pacemaker cells
Skeletal muscle
Neurons
Ca v
3.2 T Cardiac muscle Mibefradil Repetitive firing of pacemaker cells
Neurons
Ca v
3.3 T Neurons Mibefradil Repetitive firing of pacemaker cells
DHP = dihydropyridines (nifedipine). PAA = Phenylalkylamines (verapamil). BZP = benzothizeprines (diltiazem). ω-CTX = ω-conotoxin
a
Five classes of Ca 2+ channel identified as L, P/Q, N, R and T channels exist, as defined in text.
P/Q, N and R channels comprise a sub family. They are
not sensitive to L- type channels blockers and have been
shown to be involved in the regulation of transmitter
release. They are inhibited by peptide toxins including
cone snail toxins (ω-conotoxins) and spider toxins
(agatoxins).
Cyclic nucleotide–modulated channels consist of
two groups:
• the cyclic nucleotide-gated (CNG) channels, which
play important roles in sensory transduction for
olfactory and photoreceptors
• the hyperpolarization- activated, cyclic nucleotide–
gated (HCN) channels
CNG channels belong to the superfamily of
pore- loop channels for cations and share domain
structure with HCG channels and Eag- like K + channels.
Activation of CNG channels involves the binding
of cGMP or cAMP to the C terminal region of the
channel protein. These channels are multimeric channels
composed of A and B subunits. Each subunit can
bind a single molecule of cAMP or cGMP. The HCN
channels are cation channels that open with hyperpolarization
and close with depolarization; upon direct
binding of cyclic AMP or cyclic GMP, the activation
curves for the channels are shifted to more hyperpolarized
potentials. These channels play essential roles in
cardiac pacemaker cells and presumably in rhythmically
discharging neurons. Similar channels respond
to Ca 2+ /calmodulin (Biel and Michelakis, 2009).
Activation of these channels offers a therapeutic target
for the treatment of hyperalgesia seen following spinal
cord ligation.