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Receptor activity- modifying protein 1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Voltage- dependent L-type calcium channel subunit beta-4 Voltage- dependent L-type calcium channel subunit beta-1 Calcitonin gene-related peptide 1 Calcitonin gene-related peptide 1 Calcitonin gene-related peptide type 1 receptor Glutamate [NMDA] receptor subunit epsilon-1 Glutamate [NMDA] receptor subunit epsilon-2 Glutamate [NMDA] receptor subunit 3A Substance-P receptor Voltage- dependent calcium channel subunit alpha-2/delta-2 Voltage- dependent L-type calcium channel subunit beta-4 Voltage- dependent L-type calcium channel subunit beta-1 Calcitonin gene-related peptide 1 Vesicular glutamate transporter 3 Vesicular glutamate transporter 3 Vesicular glutamate transporter 2 Voltage- dependent N-type calcium channel subunit alpha-1B Voltage- dependent N-type calcium channel subunit alpha-1B Ziconotide Ca+ L-Glutamic acid Substance P Ca+ L-Glutamic acid Ziconotide Ca+ Ca+ Ca+ Substance P Ca+ L-Glutamic acid Substance P Hyperalgesia Hyperpolarization Pain Synaptic Vesicle Ziconotide inhibits N-type calcium channels which prevents calcium from entering the neuron and activating neurotransmitter release Synapse Due to the inhibition of Calcitonin gene-related peptide, the calcitonin gene-related peptide receptor cannot be activated The inactivation of calcitonin gene-related peptide receptors leads to hyperpolarization of neurons in the spinal cord, and therefore causes hyperalgesia. Presynaptic Neuron Postsynaptic Neuron Cytosol Postsynaptic Neuron The low concentration of calcium in the postsynaptic neuron causes hyperpolarization, which increases the membrane potential threshold, preventing depolarization Presynaptic Neuron Cytosol Ziconotide inhibits N-type calcium channels which prevents calcium from entering the cell and activating neurotransmitter release Synaptic Vesicle Synapse The low concentration of Substance P prevents the activation of Substance P receptors which prevents the depolarization of the dorsal root ganglion, causing hyperalgesia Ziconotide is injected into the dorsal horn of the spinal cord The low concentration of glutamate and substance P prevents them from activating the glumate receptors and substance P receptors Dorsal Root Ganglion
RAMP1 CACNA2D2 CACNB4 CACNB1 CALCA CALCA CALCRL GRIN2A GRIN2B GRIN3A TACR1 CACNA2D2 CACNB4 CACNB1 CALCA SLC17A8 SLC17A8 SLC17A6 CACNA1B CACNA1B Ziconotide Calcium L-Glutamic acid Substance P Calcium L-Glutamic acid Ziconotide Calcium Calcium Calcium Substance P Calcium L-Glutamic acid Substance P Hyperalgesia Hyperpolarization Pain
RAMP1 CACNA2D2 CACNB4 CACNB1 CALCA CALCA CALCRL GRIN2A GRIN2B GRIN3A TACR1 CACNA2D2 CACNB4 CACNB1 CALCA SLC17A8 SLC17A8 SLC17A6 CACNA1B CACNA1B Zicon Ca+ Glu SP Ca+ Glu Zicon Ca+ Ca+ Ca+ SP Ca+ Glu SP Hyper Hyper Pain Synaptic Vesicle Ziconotide inhibits N-type calcium channels which prevents calcium from entering the neuron and activating neurotransmitter release Synapse Due to the inhibition of Calcitonin gene-related peptide, the calcitonin gene-related peptide receptor cannot be activated The inactivation of calcitonin gene-related peptide receptors leads to hyperpolarization of neurons in the spinal cord, and therefore causes hyperalgesia. Presynaptic Neuron Postsynaptic Neuron Cytosol Postsynaptic Neuron The low concentration of calcium in the postsynaptic neuron causes hyperpolarization, which increases the membrane potential threshold, preventing depolarization Presynaptic Neuron Cytosol Ziconotide inhibits N-type calcium channels which prevents calcium from entering the cell and activating neurotransmitter release Synaptic Vesicle Synapse The low concentration of Substance P prevents the activation of Substance P receptors which prevents the depolarization of the dorsal root ganglion, causing hyperalgesia Ziconotide is injected into the dorsal horn of the spinal cord The low concentration of glutamate and substance P prevents them from activating the glumate receptors and substance P receptors Dorsal Root Ganglion
RAMP1 CACNA2D2 CACNB4 CACNB1 CALCA CALCA CALCRL GRIN2A GRIN2B GRIN3A TACR1 CACNA2D2 CACNB4 CACNB1 CALCA SLC17A8 SLC17A8 SLC17A6 CACNA1B CACNA1B Zicon Ca2+ Glu SP Ca2+ Glu Zicon Ca2+ Ca2+ Ca2+ SP Ca2+ Glu SP Hyper Hyper Pain