The Experts below are selected from a list of 28134 Experts worldwide ranked by ideXlab platform
Jörg W Wegener - One of the best experts on this subject based on the ideXlab platform.
-
Mouse models to study L-Type Calcium Channel function
Pharmacology & therapeutics, 2005Co-Authors: Sven Moosmang, Franz Hofmann, Peter Lenhardt, Nicole Haider, Jörg W WegenerAbstract:Calcium influx through voltage gated L-Type Ca2+ Channels has evolved as one of the most widely used transmembrane signalling mechanisms in eukaryotic organisms. Although pharmacological inhibitors of L-Type Ca2+ Channels have an important place in medical therapy, the full therapeutic potential of the 4 L-Type Ca2+ Channel subtypes has not been explored yet. To dissect the physiological relevance of the L-Type Ca2+ Channel subtype diversity, gene-targeted mouse models carrying deletions of these Channels ("knockout mice") have been generated. This review focuses on recent data from studies in mice lacking the Ca(v)1.2 and Ca(v)1.3 pore subunits, which have elucidated some of the roles of L-Type Ca2+ Channels as mediators of signalling between cell membrane and intracellular processes like blood pressure regulation, smooth muscle contractility, insulin secretion, cardiac development, and learning and memory.
-
an essential role of cav1 2 l type Calcium Channel for urinary bladder function
The FASEB Journal, 2004Co-Authors: Jörg W Wegener, Verena Schulla, Sven Moosmang, Andrea Welling, Thomas Kleppisch, Norbert Klugbauer, Susanne Feil, Robert Feil, A. Koller, Franz HofmannAbstract:SPECIFIC AIMSTo clarify the contribution of L-Type Ca2+ Channels to smooth muscle function, we inactivated the murine smooth muscle L-Type Cav1.2 Ca2+ Channel by a conditional and time-controlled k...
-
an essential role of cav1 2 l type Calcium Channel for urinary bladder function
The FASEB Journal, 2004Co-Authors: Jörg W Wegener, Verena Schulla, Sven Moosmang, Thomas Kleppisch, Norbert Klugbauer, Susanne Feil, Robert Feil, A. Koller, Taeseong Lee, Andrea WellingAbstract:Mice deficient in the smooth muscle Cav1.2 Calcium Channel (SMACKO, smooth muscle alpha1c-subunit Calcium Channel knockout) have a severely reduced micturition and an increased bladder mass. L-Type Calcium current, protein, and spontaneous contractile activity were absent in the bladder of SMACKO mice. K+ and carbachol (CCh)-induced contractions were reduced to 10-fold in detrusor muscles from SMACKO mice. The dihydropyridine isradipine inhibited K+- and CCh-induced contractions of muscles from CTR but had no effect in muscles from SMACKO mice. CCh-induced contraction was blocked by removing extracellular Ca2+ but was unaffected by the PLC inhibitor U73122 or depletion of intracellular Ca2+ stores by thapsigargin. In muscles from CTR and SMACKO mice, CCh-induced contraction was partially inhibited by the Rho-kinase inhibitor Y27632. These results show that the Cav1.2 Ca2+ Channel is essential for normal bladder function. The Rho-kinase and Ca2+-release pathways cannot compensate the lack of the L-Type Ca2+ Channel.
Sven Moosmang - One of the best experts on this subject based on the ideXlab platform.
-
Mouse models to study L-Type Calcium Channel function
Pharmacology & therapeutics, 2005Co-Authors: Sven Moosmang, Franz Hofmann, Peter Lenhardt, Nicole Haider, Jörg W WegenerAbstract:Calcium influx through voltage gated L-Type Ca2+ Channels has evolved as one of the most widely used transmembrane signalling mechanisms in eukaryotic organisms. Although pharmacological inhibitors of L-Type Ca2+ Channels have an important place in medical therapy, the full therapeutic potential of the 4 L-Type Ca2+ Channel subtypes has not been explored yet. To dissect the physiological relevance of the L-Type Ca2+ Channel subtype diversity, gene-targeted mouse models carrying deletions of these Channels ("knockout mice") have been generated. This review focuses on recent data from studies in mice lacking the Ca(v)1.2 and Ca(v)1.3 pore subunits, which have elucidated some of the roles of L-Type Ca2+ Channels as mediators of signalling between cell membrane and intracellular processes like blood pressure regulation, smooth muscle contractility, insulin secretion, cardiac development, and learning and memory.
-
an essential role of cav1 2 l type Calcium Channel for urinary bladder function
The FASEB Journal, 2004Co-Authors: Jörg W Wegener, Verena Schulla, Sven Moosmang, Andrea Welling, Thomas Kleppisch, Norbert Klugbauer, Susanne Feil, Robert Feil, A. Koller, Franz HofmannAbstract:SPECIFIC AIMSTo clarify the contribution of L-Type Ca2+ Channels to smooth muscle function, we inactivated the murine smooth muscle L-Type Cav1.2 Ca2+ Channel by a conditional and time-controlled k...
-
an essential role of cav1 2 l type Calcium Channel for urinary bladder function
The FASEB Journal, 2004Co-Authors: Jörg W Wegener, Verena Schulla, Sven Moosmang, Thomas Kleppisch, Norbert Klugbauer, Susanne Feil, Robert Feil, A. Koller, Taeseong Lee, Andrea WellingAbstract:Mice deficient in the smooth muscle Cav1.2 Calcium Channel (SMACKO, smooth muscle alpha1c-subunit Calcium Channel knockout) have a severely reduced micturition and an increased bladder mass. L-Type Calcium current, protein, and spontaneous contractile activity were absent in the bladder of SMACKO mice. K+ and carbachol (CCh)-induced contractions were reduced to 10-fold in detrusor muscles from SMACKO mice. The dihydropyridine isradipine inhibited K+- and CCh-induced contractions of muscles from CTR but had no effect in muscles from SMACKO mice. CCh-induced contraction was blocked by removing extracellular Ca2+ but was unaffected by the PLC inhibitor U73122 or depletion of intracellular Ca2+ stores by thapsigargin. In muscles from CTR and SMACKO mice, CCh-induced contraction was partially inhibited by the Rho-kinase inhibitor Y27632. These results show that the Cav1.2 Ca2+ Channel is essential for normal bladder function. The Rho-kinase and Ca2+-release pathways cannot compensate the lack of the L-Type Ca2+ Channel.
Franz Hofmann - One of the best experts on this subject based on the ideXlab platform.
-
an essential role of cav1 2 l type Calcium Channel for urinary bladder function
The FASEB Journal, 2004Co-Authors: Jörg W Wegener, Verena Schulla, Sven Moosmang, Andrea Welling, Thomas Kleppisch, Norbert Klugbauer, Susanne Feil, Robert Feil, A. Koller, Franz HofmannAbstract:SPECIFIC AIMSTo clarify the contribution of L-Type Ca2+ Channels to smooth muscle function, we inactivated the murine smooth muscle L-Type Cav1.2 Ca2+ Channel by a conditional and time-controlled k...
-
The IVS6 segment of the L-Type Calcium Channel is critical for the action of dihydropyridines and phenylalkylamines.
The EMBO journal, 1996Co-Authors: Angela Schuster, Norbert Klugbauer, Lenka Lacinová, H. Ito, L. Birnbaumer, Franz HofmannAbstract:The current through the L-Type Calcium Channel is inhibited and stimulated by distinct dihydropyridines at very low concentrations. The molecular determinants for the high affinity block and stimulation were investigated using chimeras between the class C and E Calcium Channels. Mutation of three amino acids in the last putative transmembrane segment (IVS6) of the alpha1C subunit decreased the affinity for (+)isradipine 100-fold without significantly affecting the basic properties of the expressed Channel. Mutation of two of these three amino acids completely abolished the stimulatory effect of the Calcium Channel agonist Bay K 8644. These mutations only slightly affected the blocking efficacy of mibefradil and the phenylalkylamine devapamil. Three distinct but adjacently located amino acids mediated the high affinity block by devapamil. These results suggest that the IVS6 segment of the alpha1C subunit is critical for the high affinity interaction between the L-Type Calcium Channel and the Calcium Channel agonist Bay K 8644 and the two antagonists isradipine and devapamil.
Andrea Welling - One of the best experts on this subject based on the ideXlab platform.
-
an essential role of cav1 2 l type Calcium Channel for urinary bladder function
The FASEB Journal, 2004Co-Authors: Jörg W Wegener, Verena Schulla, Sven Moosmang, Andrea Welling, Thomas Kleppisch, Norbert Klugbauer, Susanne Feil, Robert Feil, A. Koller, Franz HofmannAbstract:SPECIFIC AIMSTo clarify the contribution of L-Type Ca2+ Channels to smooth muscle function, we inactivated the murine smooth muscle L-Type Cav1.2 Ca2+ Channel by a conditional and time-controlled k...
-
an essential role of cav1 2 l type Calcium Channel for urinary bladder function
The FASEB Journal, 2004Co-Authors: Jörg W Wegener, Verena Schulla, Sven Moosmang, Thomas Kleppisch, Norbert Klugbauer, Susanne Feil, Robert Feil, A. Koller, Taeseong Lee, Andrea WellingAbstract:Mice deficient in the smooth muscle Cav1.2 Calcium Channel (SMACKO, smooth muscle alpha1c-subunit Calcium Channel knockout) have a severely reduced micturition and an increased bladder mass. L-Type Calcium current, protein, and spontaneous contractile activity were absent in the bladder of SMACKO mice. K+ and carbachol (CCh)-induced contractions were reduced to 10-fold in detrusor muscles from SMACKO mice. The dihydropyridine isradipine inhibited K+- and CCh-induced contractions of muscles from CTR but had no effect in muscles from SMACKO mice. CCh-induced contraction was blocked by removing extracellular Ca2+ but was unaffected by the PLC inhibitor U73122 or depletion of intracellular Ca2+ stores by thapsigargin. In muscles from CTR and SMACKO mice, CCh-induced contraction was partially inhibited by the Rho-kinase inhibitor Y27632. These results show that the Cav1.2 Ca2+ Channel is essential for normal bladder function. The Rho-kinase and Ca2+-release pathways cannot compensate the lack of the L-Type Ca2+ Channel.
Albert S. Chang - One of the best experts on this subject based on the ideXlab platform.
-
Gestational Changes in Uterine L-Type Calcium Channel Function and Expression in Guinea Pig
Biology of reproduction, 2000Co-Authors: Patricia L. Collins, John J. Moore, David W. Lundgren, Elena Choobineh, Sharon M. Chang, Albert S. ChangAbstract:Abstract Pregnancy can influence both the resting membrane potential and the ion Channel composition of the uterine myometrium. Calcium flux is essential for excitation-contraction coupling in pregnant uterus. The uterine L-Type Calcium Channel is an important component in mediating Calcium flux and is purported to play a role in parturition. This study was undertaken to characterize gestational changes in 1) the uterine contractile response to the L-Type Calcium Channel agonist, Bay K 8644; 2) the mRNA expression of Channel subunits by semiquantitative reverse transcriptase-polymerase chain reaction; and 3) estimate Channel protein levels by measuring 3H-isradipine binding at the dihydropyridine binding site of the α1c subunit utilizing saturation binding methods. Sensitivity to Bay K 8644 increases beginning at 0.8 of gestation and persists through term. The change in sensitivity is coincident with an increased mRNA expression of the α1c and β2 subunits but with the least detectable amounts of isradipin...
-
Gestational Changes in Uterine L-Type Calcium Channel Function and Expression in Guinea Pig
Biology of reproduction, 2000Co-Authors: Patricia L. Collins, John J. Moore, David W. Lundgren, Elena Choobineh, Sharon M. Chang, Albert S. ChangAbstract:Pregnancy can influence both the resting membrane potential and the ion Channel composition of the uterine myometrium. Calcium flux is essential for excitation-contraction coupling in pregnant uterus. The uterine L-Type Calcium Channel is an important component in mediating Calcium flux and is purported to play a role in parturition. This study was undertaken to characterize gestational changes in 1) the uterine contractile response to the L-Type Calcium Channel agonist, Bay K 8644; 2) the mRNA expression of Channel subunits by semiquantitative reverse transcriptase-polymerase chain reaction; and 3) estimate Channel protein levels by measuring (3)H-isradipine binding at the dihydropyridine binding site of the alpha(1c) subunit utilizing saturation binding methods. Sensitivity to Bay K 8644 increases beginning at 0.8 of gestation and persists through term. The change in sensitivity is coincident with an increased mRNA expression of the alpha(1c) and beta(2) subunits but with the least detectable amounts of isradipine binding. The expressed alpha(1c) transcript represents a novel structural variant with a 118-amino acid deletion in the III-IV linker and repeats IVS1-S3 of the protein sequence. The guinea pig uterine L-Type Calcium Channel activity is highly regulated through gestation, but the regulation of mRNA expression may be different from regulation of protein levels, estimated by isradipine binding. The up-regulation of function, alpha(1c) subunit mRNA expression, and isradipine binding at term gestation are consistent with a role for this ion Channel in parturition.
