Todd Scheuer

Voltage-gated ion channels and gating modifier toxins. (2007)

Catterall, William, Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Yu, Frank, Konoki, Keiichi, Scheuer, Todd

Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent...

Voltage-gated ion channels and gating modifier toxins. (2007)

Catterall, William, Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Yu, Frank, Konoki, Keiichi, Scheuer, Todd

Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent...

Voltage-gated ion channels and gating modifier toxins. (2007)

Catterall, William, Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Yu, Frank, Konoki, Keiichi, Scheuer, Todd

Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent...

Voltage-gated ion channels and gating modifier toxins. (2007)

Catterall, William, Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Yu, Frank, Konoki, Keiichi, Scheuer, Todd

Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent...

Voltage-gated ion channels and gating modifier toxins. (2007)

Catterall, William, Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Yu, Frank, Konoki, Keiichi, Scheuer, Todd

Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent...

Voltage-gated ion channels and gating modifier toxins. (2007)

Catterall, William, Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Yu, Frank, Konoki, Keiichi, Scheuer, Todd

Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent...

Voltage-gated ion channels and gating modifier toxins. (2007)

Catterall, William, Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Yu, Frank, Konoki, Keiichi, Scheuer, Todd

Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent...

Voltage-gated ion channels and gating modifier toxins. (2007)

Catterall, William, Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Yu, Frank, Konoki, Keiichi, Scheuer, Todd

Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent...

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. (2006)

Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Qu, Yusheng, Sampieri, François, Scheuer, Todd, Catterall, William

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor...

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. (2006)

Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Qu, Yusheng, Sampieri, François, Scheuer, Todd, Catterall, William

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor...

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. (2006)

Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Qu, Yusheng, Sampieri, François, Scheuer, Todd, Catterall, William

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor...

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. (2006)

Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Qu, Yusheng, Sampieri, François, Scheuer, Todd, Catterall, William

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor...

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. (2006)

Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Qu, Yusheng, Sampieri, François, Scheuer, Todd, Catterall, William

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor...

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. (2006)

Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Qu, Yusheng, Sampieri, François, Scheuer, Todd, Catterall, William

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor...

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. (2006)

Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Qu, Yusheng, Sampieri, François, Scheuer, Todd, Catterall, William

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor...

Structure and function of the voltage sensor of sodium channels probed by a beta-scorpion toxin. (2006)

Cestèle, Sandrine, Yarov-Yarovoy, Vladimir, Qu, Yusheng, Sampieri, François, Scheuer, Todd, Catterall, William

Voltage sensing by voltage-gated sodium channels determines the electrical excitability of cells, but the molecular mechanism is unknown. beta-Scorpion toxins bind specifically to neurotoxin receptor...

Inhibition of cardiac L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain

McHugh, Damian, Sharp, Elizabeth M., Scheuer, Todd, Catterall, William A.

We have investigated the mechanism underlying the modulation of the cardiac L-type Ca2+ current by protein kinase C (PKC). Using the patch-clamp technique, we found that PKC activation by...

Potent blockade of sodium channels and protection of brain tissue from ischemia by BIII 890 CL

Carter, Adrian J., Grauert, Matthias, Pschorn, Uwe, Bechtel, Wolf Dietrich, Bartmann-Lindholm, Christina, Qu, Yusheng, ...

We have synthesized a new benzomorphan derivative, 2R-[2α,3(S*),6α]-1,2,3,4,5,6-hexahydro-6,11,11-trimethyl-3-[2-(phenylmethoxy)propyl]-2,6-methano-3-benzazocin-10-ol hydrochloride (BIII 890 CL),...

Molecular determinants of inactivation and G protein modulation in the intracellular loop connecting domains I and II of the calcium channel α1A subunit

Herlitze, Stefan, Hockerman, Gregory H., Scheuer, Todd, Catterall, William A.

Synaptic transmission is regulated by G protein-coupled receptors whose activation releases G protein βγ subunits that modulate presynaptic Ca2+ channels. The sequence motif QXXER has been proposed...

Type II regulatory subunits are not required for the anchoring-dependent modulation of Ca2+ channel activity by cAMP-dependent protein kinase

Burton, Kimberly A., Johnson, Barry D., Hausken, Zachary E., Westenbroek, Ruth E., Idzerda, Rejean L., Scheuer, Todd, ...

Preferential phosphorylation of specific proteins by cAMP-dependent protein kinase (PKA) may be mediated in part by the anchoring of PKA to a family of A-kinase anchor proteins (AKAPs) positioned in...

Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel

Linford, Nancy J., Cantrell, Angela R., Qu, Yusheng, Scheuer, Todd, Catterall, William A.

The voltage-gated sodium channel is the site of action of more than six classes of neurotoxins and drugs that alter its function by interaction with distinct, allosterically coupled receptor sites....

Construction of a high-affinity receptor site for dihydropyridine agonists and antagonists by single amino acid substitutions in a non-l-type Ca2+ channel

Hockerman, Gregory H., Peterson, Blaise Z., Sharp, Elizabeth, Tanada, Timothy N., Scheuer, Todd, Catterall, William A.

The activity of l-type Ca2+ channels is increased by dihydropyridine (DHP) agonists and inhibited by DHP antagonists, which are widely used in the therapy of cardiovascular disease. These drugs bind...

Allosteric modulation of Ca2+ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Cavβ subunits

Herlitze, Stefan, Zhong, Huijun, Scheuer, Todd, Catterall, William A.

N-type and P/Q-type Ca2+ channels are inhibited by neurotransmitters acting through G protein-coupled receptors in a membrane-delimited pathway involving Gβγ subunits. Inhibition is caused by a...

Control of gating mode by a single amino acid residue in transmembrane segment IS3 of the N-type Ca2+ channel

Zhong, Huijun, Li, Bin, Scheuer, Todd, Catterall, William A.

N-type Ca2+ channels can be inhibited by neurotransmitter-induced release of G protein βγ subunits. Two isoforms of Cav2.2 α1 subunits of N-type calcium channels from rat brain (Cav2.2a and...

Role of the C-terminal domain in inactivation of brain and cardiac sodium channels

Mantegazza, Massimo, Yu, Frank H., Catterall, William A., Scheuer, Todd

Inactivation is a fundamental characteristic of Na+ channels, and small changes cause skeletal muscle paralysis and myotonia, epilepsy, and cardiac arrhythmia. Brain Nav1.2a channels have faster...

An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart

Maier, Sebastian K. G., Westenbroek, Ruth E., Schenkman, Kenneth A., Feigl, Eric O., Scheuer, Todd, Catterall, William A.

Voltage-gated sodium channels composed of pore-forming α and auxiliary β subunits are responsible for the rising phase of the action potential in cardiac muscle, but the functional roles of...

Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel β2-subunits

Chen, Chunling, Bharucha, Vandana, Chen, Yuan, Westenbroek, Ruth E., Brown, Angus, Malhotra, Jyoti Dhar, ...

Sodium channel β-subunits modulate channel gating, assembly, and cell surface expression in heterologous cell systems. We generated β2−/− mice to investigate the role of β2 in control of...

Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels

Mochida, Sumiko, Westenbroek, Ruth E., Yokoyama, Charles T., Zhong, Huijun, Myers, Scott J., Scheuer, Todd, ...

Cav2.1 channels, which conduct P/Q-type Ca2+ currents, were expressed in superior cervical ganglion neurons in cell culture, and neurotransmission initiated by these exogenously expressed Ca2+...

An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node

Maier, Sebastian K. G., Westenbroek, Ruth E., Yamanushi, T. T., Dobrzynski, H., Boyett, Mark R., Catterall, William A., ...

Voltage-gated Na+ channels are composed of pore-forming α and auxiliary β subunits. The majority of Na+ channels in the heart contain tetrodotoxin (TTX)-insensitive Nav1.5 α subunits, but...

β-Adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2 channels via a leucine zipper interaction with A kinase-anchoring protein 15

Hulme, Joanne T., Lin, Teddy W.-C., Westenbroek, Ruth E., Scheuer, Todd, Catterall, William A.

Activation of β-adrenergic receptors and consequent phosphorylation by cAMP-dependent protein kinase A (PKA) greatly increases the L-type Ca2+ current through CaV1.2 channels in isolated cardiac...

Molecular determinants of Ca2+/calmodulin-dependent regulation of Cav2.1 channels

Lee, Amy, Zhou, Hong, Scheuer, Todd, Catterall, William A.

Ca2+-dependent facilitation and inactivation (CDF and CDI) of Cav2.1 channels modulate presynaptic P/Q-type Ca2+ currents and contribute to activity-dependent synaptic plasticity. This dual feedback...

Reversed voltage-dependent gating of a bacterial sodium channel with proline substitutions in the S6 transmembrane segment

Zhao, Yong, Scheuer, Todd, Catterall, William A.

Members of the voltage-gated-like ion channel superfamily have a conserved pore structure. Transmembrane helices that line the pore (M2 or S6) are thought to gate it at the cytoplasmic end by bending...

Convergent regulation of skeletal muscle Ca2+ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Johnson, Barry D., Scheuer, Todd, Catterall, William A.

The skeletal muscle L-type Ca2+ channel (CaV1.1), which is responsible for initiating muscle contraction, is regulated by phosphorylation by cAMP-dependent protein kinase (PKA) in a voltage-dependent...

Differential modulation of Cav2.1 channels by calmodulin and Ca2+-binding protein 1

Lee, Amy, Westenbroek, Ruth E., Haeseleer, Françoise, Palczewski, Krzysztof, Scheuer, Todd, Catterall, William A.

Cav2.1 channels, which mediate P/Q-type Ca2+ currents, undergo Ca2+/calmodulin (CaM)-dependent inactivation and facilitation that can significantly alter synaptic efficacy. Here we report that the...

Inhibition of cardiac L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain

McHugh, Damian, Sharp, Elizabeth M., Scheuer, Todd, Catterall, William A.

We have investigated the mechanism underlying the modulation of the cardiac L-type Ca2+ current by protein kinase C (PKC). Using the patch-clamp technique, we found that PKC activation by...

Potent blockade of sodium channels and protection of brain tissue from ischemia by BIII 890 CL

Carter, Adrian J., Grauert, Matthias, Pschorn, Uwe, Bechtel, Wolf Dietrich, Bartmann-Lindholm, Christina, Qu, Yusheng, ...

We have synthesized a new benzomorphan derivative, 2R-[2α,3(S*),6α]-1,2,3,4,5,6-hexahydro-6,11,11-trimethyl-3-[2-(phenylmethoxy)propyl]-2,6-methano-3-benzazocin-10-ol hydrochloride (BIII 890 CL),...

Molecular determinants of inactivation and G protein modulation in the intracellular loop connecting domains I and II of the calcium channel α1A subunit

Herlitze, Stefan, Hockerman, Gregory H., Scheuer, Todd, Catterall, William A.

Synaptic transmission is regulated by G protein-coupled receptors whose activation releases G protein βγ subunits that modulate presynaptic Ca2+ channels. The sequence motif QXXER has been proposed...

Type II regulatory subunits are not required for the anchoring-dependent modulation of Ca2+ channel activity by cAMP-dependent protein kinase

Burton, Kimberly A., Johnson, Barry D., Hausken, Zachary E., Westenbroek, Ruth E., Idzerda, Rejean L., Scheuer, Todd, ...

Preferential phosphorylation of specific proteins by cAMP-dependent protein kinase (PKA) may be mediated in part by the anchoring of PKA to a family of A-kinase anchor proteins (AKAPs) positioned in...

Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel

Linford, Nancy J., Cantrell, Angela R., Qu, Yusheng, Scheuer, Todd, Catterall, William A.

The voltage-gated sodium channel is the site of action of more than six classes of neurotoxins and drugs that alter its function by interaction with distinct, allosterically coupled receptor sites....

Construction of a high-affinity receptor site for dihydropyridine agonists and antagonists by single amino acid substitutions in a non-l-type Ca2+ channel

Hockerman, Gregory H., Peterson, Blaise Z., Sharp, Elizabeth, Tanada, Timothy N., Scheuer, Todd, Catterall, William A.

The activity of l-type Ca2+ channels is increased by dihydropyridine (DHP) agonists and inhibited by DHP antagonists, which are widely used in the therapy of cardiovascular disease. These drugs bind...

Allosteric modulation of Ca2+ channels by G proteins, voltage-dependent facilitation, protein kinase C, and Cavβ subunits

Herlitze, Stefan, Zhong, Huijun, Scheuer, Todd, Catterall, William A.

N-type and P/Q-type Ca2+ channels are inhibited by neurotransmitters acting through G protein-coupled receptors in a membrane-delimited pathway involving Gβγ subunits. Inhibition is caused by a...

Control of gating mode by a single amino acid residue in transmembrane segment IS3 of the N-type Ca2+ channel

Zhong, Huijun, Li, Bin, Scheuer, Todd, Catterall, William A.

N-type Ca2+ channels can be inhibited by neurotransmitter-induced release of G protein βγ subunits. Two isoforms of Cav2.2 α1 subunits of N-type calcium channels from rat brain (Cav2.2a and...

Role of the C-terminal domain in inactivation of brain and cardiac sodium channels

Mantegazza, Massimo, Yu, Frank H., Catterall, William A., Scheuer, Todd

Inactivation is a fundamental characteristic of Na+ channels, and small changes cause skeletal muscle paralysis and myotonia, epilepsy, and cardiac arrhythmia. Brain Nav1.2a channels have faster...

An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart

Maier, Sebastian K. G., Westenbroek, Ruth E., Schenkman, Kenneth A., Feigl, Eric O., Scheuer, Todd, Catterall, William A.

Voltage-gated sodium channels composed of pore-forming α and auxiliary β subunits are responsible for the rising phase of the action potential in cardiac muscle, but the functional roles of...

Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel β2-subunits

Chen, Chunling, Bharucha, Vandana, Chen, Yuan, Westenbroek, Ruth E., Brown, Angus, Malhotra, Jyoti Dhar, ...

Sodium channel β-subunits modulate channel gating, assembly, and cell surface expression in heterologous cell systems. We generated β2−/− mice to investigate the role of β2 in control of...

Requirement for the synaptic protein interaction site for reconstitution of synaptic transmission by P/Q-type calcium channels

Mochida, Sumiko, Westenbroek, Ruth E., Yokoyama, Charles T., Zhong, Huijun, Myers, Scott J., Scheuer, Todd, ...

Cav2.1 channels, which conduct P/Q-type Ca2+ currents, were expressed in superior cervical ganglion neurons in cell culture, and neurotransmission initiated by these exogenously expressed Ca2+...

An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node

Maier, Sebastian K. G., Westenbroek, Ruth E., Yamanushi, T. T., Dobrzynski, H., Boyett, Mark R., Catterall, William A., ...

Voltage-gated Na+ channels are composed of pore-forming α and auxiliary β subunits. The majority of Na+ channels in the heart contain tetrodotoxin (TTX)-insensitive Nav1.5 α subunits, but...

β-Adrenergic regulation requires direct anchoring of PKA to cardiac CaV1.2 channels via a leucine zipper interaction with A kinase-anchoring protein 15

Hulme, Joanne T., Lin, Teddy W.-C., Westenbroek, Ruth E., Scheuer, Todd, Catterall, William A.

Activation of β-adrenergic receptors and consequent phosphorylation by cAMP-dependent protein kinase A (PKA) greatly increases the L-type Ca2+ current through CaV1.2 channels in isolated cardiac...

Molecular determinants of Ca2+/calmodulin-dependent regulation of Cav2.1 channels

Lee, Amy, Zhou, Hong, Scheuer, Todd, Catterall, William A.

Ca2+-dependent facilitation and inactivation (CDF and CDI) of Cav2.1 channels modulate presynaptic P/Q-type Ca2+ currents and contribute to activity-dependent synaptic plasticity. This dual feedback...

Reversed voltage-dependent gating of a bacterial sodium channel with proline substitutions in the S6 transmembrane segment

Zhao, Yong, Scheuer, Todd, Catterall, William A.

Members of the voltage-gated-like ion channel superfamily have a conserved pore structure. Transmembrane helices that line the pore (M2 or S6) are thought to gate it at the cytoplasmic end by bending...

Convergent regulation of skeletal muscle Ca2+ channels by dystrophin, the actin cytoskeleton, and cAMP-dependent protein kinase

Johnson, Barry D., Scheuer, Todd, Catterall, William A.

The skeletal muscle L-type Ca2+ channel (CaV1.1), which is responsible for initiating muscle contraction, is regulated by phosphorylation by cAMP-dependent protein kinase (PKA) in a voltage-dependent...

Phosphorylation of serine 1928 in the distal C-terminal domain of cardiac CaV1.2 channels during β1-adrenergic regulation

Hulme, Joanne T., Westenbroek, Ruth E., Scheuer, Todd, Catterall, William A.

During the fight-or-flight response, epinephrine and norepinephrine released by the sympathetic nervous system increase L-type calcium currents conducted by CaV1.2a channels in the heart, which...

Dopamine modulation of neuronal Na+ channels requires binding of A kinase-anchoring protein 15and PKA by a modified leucine zipper motif

Few, W. Preston, Scheuer, Todd, Catterall, William A.

In hippocampal pyramidal cells, dopamine acts at D1 receptors to reduce peak Na+ currents by activation of phosphorylation by PKA anchored via an A kinase-anchoring protein (AKAP15). However, the...

Autoinhibitory control of the CaV1.2 channel by its proteolytically processed distal C-terminal domain

Hulme, Joanne T, Yarov-Yarovoy, Vladimir, Lin, Teddy W-C, Scheuer, Todd, Catterall, William A

Voltage-gated Ca2+ channels of the CaV1 family initiate excitation–contraction coupling in cardiac, smooth, and skeletal muscle and are primary targets for regulation by the sympathetic nervous...

Modulation of CaV1.2 Channels by Mg2+ Acting at an EF-hand Motif in the COOH-terminal Domain

Brunet, Sylvain, Scheuer, Todd, Klevit, Rachel, Catterall, William A.

Magnesium levels in cardiac myocytes change in cardiovascular diseases. Intracellular free magnesium (Mgi) inhibits L-type Ca2+ currents through CaV1.2 channels in cardiac myocytes, but the mechanism...

Neutralization of Gating Charges in Domain II of the Sodium Channel α Subunit Enhances Voltage-Sensor Trapping by a β-Scorpion Toxin

Cestèle, Sandrine, Scheuer, Todd, Mantegazza, Massimo, Rochat, Hervé, Catterall, William A.

β-Scorpion toxins shift the voltage dependence of activation of sodium channels to more negative membrane potentials, but only after a strong depolarizing prepulse to fully activate the channels....

Molecular Analysis of the Putative Inactivation Particle in the Inactivation Gate of Brain Type IIA Na+ Channels

Kellenberger, Stephan, West, James W., Scheuer, Todd, Catterall, William A.

Fast Na+ channel inactivation is thought to involve binding of phenylalanine 1489 in the hydrophobic cluster IFM in LIII-IV of the rat brain type IIA Na+ channel. We have analyzed macroscopic and...

Molecular Analysis of Potential Hinge Residues in the Inactivation Gate of Brain Type IIA Na+ Channels

Kellenberger, Stephan, West, James W., Catterall, William A., Scheuer, Todd

During inactivation of Na+ channels, the intracellular loop connecting domains III and IV is thought to fold into the channel protein and occlude the pore through interaction of the hydrophobic motif...

Increased Expression of the Cardiac L-type Calcium Channel in Estrogen Receptor–deficient Mice

Johnson, Barry D., Zheng, Wei, Korach, Kenneth S., Scheuer, Todd, Catterall, William A., Rubanyi, Gabor M.

Steroid hormones control the expression of many cellular regulators, and a role for estrogen in cardiovascular function and disease has been well documented. To address whether the activity of the...

Modulation of CaV2.1 channels by Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain

Jiang, Xin, Lautermilch, Nathan J., Watari, Hirofumi, Westenbroek, Ruth E., Scheuer, Todd, Catterall, William A.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of synaptic responses in the postsynaptic density, but understanding of its mechanisms of action in the presynaptic neuron is...

Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation

DeCaen, Paul G., Yarov-Yarovoy, Vladimir, Zhao, Yong, Scheuer, Todd, Catterall, William A.

The S4 transmembrane segments of voltage-gated ion channels move outward on depolarization, initiating a conformational change that opens the pore, but the mechanism of S4 movement is unresolved. One...

Depolarization-activated gating pore current conducted by mutant sodium channels in potassium-sensitive normokalemic periodic paralysis

Sokolov, Stanislav, Scheuer, Todd, Catterall, William A.

Some inherited periodic paralyses are caused by mutations in skeletal muscle NaV1.4 sodium channels that alter channel gating and impair action potential generation. In the case of hypokalemic...

Temperature- and age-dependent seizures in a mouse model of severe myoclonic epilepsy in infancy

Oakley, John C., Kalume, Franck, Yu, Frank H., Scheuer, Todd, Catterall, William A.

Heterozygous loss-of-function mutations in the α subunit of the type I voltage-gated sodium channel NaV1.1 cause severe myoclonic epilepsy in infancy (SMEI), an infantile-onset epileptic...

Cooperative regulation of Cav1.2 channels by intracellular Mg2+, the proximal C-terminal EF-hand, and the distal C-terminal domain

Brunet, Sylvain, Scheuer, Todd, Catterall, William A.

L-type Ca2+ currents conducted by Cav1.2 channels initiate excitation–contraction coupling in cardiac myocytes. Intracellular Mg2+ (Mgi) inhibits the ionic current of Cav1.2 channels. Because Mgi...

Sequential formation of ion pairs during activation of a sodium channel voltage sensor

DeCaen, Paul G., Yarov-Yarovoy, Vladimir, Sharp, Elizabeth M., Scheuer, Todd, Catterall, William A.

Electrical signaling in biology depends upon a unique electromechanical transduction process mediated by the S4 segments of voltage-gated ion channels. These transmembrane segments are driven outward...