F Hofmann

..The complete Compendium, including data tables for each member of the cyclic nucleotide-modulated channel family can be found at http://www.iuphar-db.org/iuphar-ic/...

..These data show that cGKs are signaling molecules involved in many biological functions...

..We conclude that the expressed alpha1C-a beta2a complex is sufficient to support prepulse facilitation. Facilitation is prevented by coexpression of the alpha2delta subunit...

..These results suggest that IRAG may be involved in cGKI-dependent and -independent pathways...

..hHCN2 and hHCN4 currents differ profoundly from each other in their activation kinetics, being fast and slow, respectively. We thus conclude that hHCN2 and hHCN4 may underlie the fast and slow component of cardiac If, respectively...

..We conclude that cGMP-dependent relaxation of hormone receptor-triggered smooth muscle contraction essentially depends on the interaction of cGKI-IRAG with IP(3)RI...

..Our results suggest that the heterogeneity of native I(h) currents is generated, at least in part, by the tissue-specific expression of HCN channel genes...

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..We have also identified full-length sequences of two related channels, HAC2 and HAC3, that are specifically expressed in the brain, indicating the existence of a family of hyperpolarization-activated cation channels...

..These results indicate that gamma1 decreases the amount of Ca(2+) entry during stimulation of skeletal muscle...

..3) knockout embryos at day 12.5 p.c. These results indicate that, up to day 14 p.c., contraction of murine embryonic hearts requires an unidentified, low affinity L-type like calcium channel...

..The kinetics of ICa inactivation were significantly slower than those of IBa. The expressed alpha1G channel has a relatively high sensitivity to mibefradil, but is only slightly affected by Ni2+...

..The results show that PLC/IP(3)-dependent Ca(2+) release is activated by stimulation with carbachol in urinary bladder smooth muscle but has a minor contribution to overall carbachol-induced Ca(2+) signals...

..2 (-/-) cardiomyocytes. In summary, our results imply that calcium channel expression is dynamically regulated during heart development and that the Cav1.3 channel may substitute for Cav1.2 during early embryogenesis...

..These results show that cGKs are not involved in LTP in mice and that NO induces LTP through an alternative cGMP-independent pathway, possibly ADP-ribosylation...

..The complete amino acid sequence of a CNG channel from rabbit aorta has been deduced by cloning and sequence analysis of the cDNA. Synthetic RNA derived from this cDNA induces the formation of a functional CNG channel in Xenopus oocytes...

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..We suggest that activation of smooth muscle cGKI contributes to the proatherogenic effect of NO and that inhibition of cGKI might be a therapeutic option for treating atherosclerosis in humans...

..The expression of various CNG4 isoforms in retina and olfactory epithelium indicates that the CNG4 subunit may be necessary for normal function of both photoreceptor and olfactory CNG channels...

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..In contrast, cGKII null mutants lack these phenotypes. Our data suggest a function of cGKI, likely the beta isoform, in the LA, supporting synaptic plasticity and consolidation of fear memory...

..The recombined genome persisted for at least four months after tamoxifen treatment. SM-CreER(T2)(ki) transgenic mice should be useful to study the effects of various somatic mutations in smooth muscle...

..These results show that cGMP induced reduction of cytosolic calcium concentrations requires cGKIbeta and phosphorylation of Ser(696) of IRAG...

..However, cGKI-deficient smooth muscle responded normally to cAMP, indicating that cAMP and cGMP signal via independent pathways, with cGKI being the specific mediator of the NO/cGMP effects in murine smooth muscle...

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..No significant difference was found for any of the examined parameters. 3. These results suggest that the LVA alpha1G channel is not regulated by known auxiliary alpha2delta subunits...

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..It is likely that CNG-3 protein is responsible for cGMP-induced Ca2+ entry in cells other than sensory cells...

..In summary, we provide evidence that cytosolic cGKI can support fear memory consolidation and LTP in neurons of the lateral amygdala via activation of CREB and CRE-dependent transcription...

..Our results strongly support the notion that CaMKII-dependent phosphorylation of Cav1.2 at S1512 and S1570 mediates Ca(2+) current facilitation in the murine heart...

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..CNG3-deficient mice provide an animal model to dissect unequivocally the contribution of rod and cone pathways for normal retinal function...

..These results indicate that cGKI in PCs is dispensable for general motor coordination, but that it is required for cerebellar LTD and specific forms of motor learning, namely the adaptation of the VOR...

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..Because both drugs are commonly used at concentrations of approximately 10 microM or higher, the interpretation of such experiments is questionable with respect to a regulatory action of PI3-K or PKC on L-type Ca(2+) channels...

..These results strongly suggest that cardiac myocyte cGKI does not affect the development of heart hypertrophy induced by pressure overload or chronic ISO infusion...

..2 protein was strongly decreased in the S1512A/S1570A double mutant. These results suggest that voltage-dependent facilitation of the Ca(v)1.2 channel depends on the phosphorylation of Ser1512/Ser1570 by calmodulin kinase II...

..2 is a substrate for PKC-mediated phosphorylation. These findings suggest that a signaling complex consisting of Ca(V)1.2, PKC, and, probably, PLD controls muscarinic-mediated phasic contraction of urinary bladder smooth muscle...

..The effect of 8-Br-cGMP on U-46619-induced contraction was attenuated by PKI 5-24. These results show that cGKI has only a small inhibitory effect on Ca(2+) sensitization in murine aortas...

..2 by PKA. Therefore, our data show that PKA phosphorylation of Ser(1928) of Ca(v)1.2 is not functionally involved in beta-adrenergic stimulation of Ca(v)1.2-mediated Ca(2+) influx into the cardiomyocyte...

..In summary, these results show that cGKIalpha down-regulates Ca2+ transients and chemotaxis in murine neutrophils. The regulatory influences of cGKIalpha on the secretagogue responses are complex, depending on the granule subtype...

..These results support the view that cGKII modulates aldosterone secretion in the murine adrenal cortex...

..The genomic clustering of both transporters, typical also for other members of the ABC family, supports the notion that ABC-C may be involved in development of resistance to xenobiotics...

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..These results demonstrate that the mutations of Ch30 affect selectively the high affinity inhibition of an inactivated channel and unmask a low affinity interaction of isradipine with an open state of the channel...

..The coexpression of the gamma-5 subunit accelerates the time course of current activation and inactivation of the alpha(1G) T-type calcium channel...

..The relationships between cloned HCN channel types and native cardiac I(f) currents are explored...

..Our results suggest that the higher DHP selectivity of the alpha1Cb versus the alpha1Ca channel is caused by the structural difference in the binding site and not by different transitions between resting, open and inactivated states...

..The alpha(1G) current was minimally activated by 1 microM Bay K 8644...

..In contrast, alpha2delta-1, alpha2delta-3, gamma-2 and gamma-4 subunits failed to modulate the current or had only minor effects...

..2 channel-mediated Ca2+ influx to either process...

..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...

..2SMAKO mice. These results demonstrate that the effect of the putative T-type Ca2+ channel-selective blocker mibefradil on blood pressure and small vessel myogenic tone is mediated by the Cav1.2 L-type Ca2+ channel...

..The missing response to cAMP distinguishes human HCN3 from both the well cAMP responding HCN subtypes 2 and 4 and the weak responding subtype 1...

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..Isozyme-specific inhibitors and activators of cGK and its downstream substrates might act more specifically than upstream signalling activators, such as organic nitrates and phosphodiesterase inhibitors...

..Thus, cGKs serve key functions in the transduction of cGMP signals into cellular responses in distinct regions of the nervous system.-..

..Hence, all available sinus node inhibitors possess an as-yet-unrecognized proarrhythmic potential...

..This new concept has important implications for the use of cGMP-elevating drugs in humans and might help to identify novel therapeutic strategies for vascular proliferative diseases...

..No taste differences to sweet solutions were observed compared to control animals. In summary, our data show that cGKII activity modulates anxiety-like behaviour and neurobehavioural effects of alcohol...

..These results identify a role for SM22alpha in the regulation of SMC phenotype during atherogenesis...

..Alpha2delta subunits can also support pharmacological interactions with drugs that are used for the treatment of epilepsy and neuropathic pain...

..PLB, IP(3)RI, and cGMP kinase Ibeta were co-immune precipitated after expression in COS-7 cells. These results suggest that PLB may have additional functions to regulate the activity of SERCA II...

..Our results define the physiological role of the HCN2 subunit as a major determinant of membrane resting potential that is required for regular cardiac and neuronal rhythmicity...

..3 channel has a similar affinity for nisoldipine as Ca(v)1.2+/+ cardiomyocytes, the L-type-like Ca(2+) channel found in Ca(v)1.2+/+ and -/- cardiomyocytes is not identical with the new Ca(v)1.3 splice variants...

..Activation of the NO/cGMP/cGKI pathway induces relaxation of smooth muscle by lowering the cytosolic calcium level and/or by calcium desensitization of the contractile elements...

..cGKII is involved in intestinal water secretion, bone growth and circardian rhythmicity. The cGK mutant mice are important tools to obtain detailed insights into cGMP-mediated signalling pathways in health and disease...

..Together, these results identify a novel proadhesive function of cGMP/cGKI signaling in primary VSMCs and suggest that the opposing effects of this pathway on VSMC number depend on the phenotypic context of the cells...

..Taken together our results indicate that the speed of activation of the HCN4 channel is determined by structural elements present in the S1, S1-S2 linker, and the S2 segment...

..These results suggest that one component of NO/cGMP-induced smooth muscle relaxation is the activation of the cGKIalpha isoform, which decreases the noradrenaline-stimulated cytosolic Ca(2+) level...

..These results suggest that hippocampal cGKI supports an age- and protein synthesis-dependent form of hippocampal LTP, whereas it is dispensable for hippocampus-dependent spatial reference and contextual memory...

..In conclusion, the Ca(v)1.2 channel is essential for electromechanical coupling and important for pharmaco-mechanical coupling in intestinal smooth muscle and cannot be substituted functionally by other Ca2+ entry pathways...

..These results demonstrate that hypothyroidism does not change dihydropyridine sensitivity (i.e., the pattern of Ca2+-channel expression) in the murine uterus...

..0, were not detected in HCN4-deficient embryos. Thus, HCN4 channels are essential for the proper generation of pacemaker potentials in the emerging sinoatrial node...

..2 channel. These results show that Cav1.2 calcium channels are key players in the hormonal regulation of blood pressure and development of myogenic tone...

..The purpose of this study was to examine the functional role of the smooth muscle cGMP/cGKI signaling cascade in restenosis of vessels...

..These data suggest that some of the effects of cGMP in peripheral tissues and cells might involve the activation of CNG channels...

..These results together with the known alpha 1 subunit heterogeneity, suggest that different types of calcium currents may depend on channel subunit composition...

..Thus, cGKs may represent novel drug targets for the treatment of human cardiovascular disorders...

..The cGKII-deficient mice also developed dwarfism that was caused by a severe defect in endochondral ossification at the growth plates. These results indicate that cGKII plays a central role in diverse physiological processes...

..Instead, two TTX-sensitive sodium currents were found: an early inactivating and a residual current. The residual current was only recovered in a subpopulation of B-cells. A putative genetic background for these currents is Na(v)1.7...

..2 channel. Thus, the conduit of Ca(2+) entry determines the ability of the cation to elicit secretion...

..This study assessed the feasibility and usefulness of combined PET and MRI for monitoring cell engraftment and survival after cell transplantation...

..These results demonstrate a role for cGKI signaling in cortical development related to neuronal migration/positioning that is important for dendritic orientation and connectivity...

..entla is allelic to ducky and ducky2J, representing the third murine Cacna2d2 allele identified and so far the only one encoding an untruncated protein that is incorporated into membranes...

..2 channels are involved in regulating the intrinsic excitability of CA1 pyramidal neurons. This cellular mechanism may contribute to the known function of Ca(v)1.2 channels in supporting synaptic plasticity and memory...

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..These data indicate that hypertrophic differentiation of growth plate chondrocytes during skeletal growth is promoted by phosphorylation and inactivation of GSK-3beta by cGKII...

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..In sum, we suggest NO-induced activation and phosphorylation of PDE5 as the mechanism for a long-lasting negative feedback loop shaping the cGMP response in human platelets in order to adapt to the amount of NO available...

..The cGMP-stimulated platelet responses are biphasic, consisting of an initial transient stimulatory response that promotes platelet aggregation and a subsequent inhibitory response that limits the size of thrombi...

..Our studies therefore reveal that cGMP signaling is important for axonal growth in vivo and in vitro...

..This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification...

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..These results demonstrate that cGKI mediates the negative inotropic effect of cGMP in the myocardium of juvenile and adult mice...

..Together, the data suggest that phosphorylation and activation of PDE5 by PKG I and its subsequent dephosphorylation by myosin phosphatase may be key steps in the regulation of relaxation/contraction cycles of smooth muscle...

..These results show that cGKI in smooth muscle is essential and that either cGKI isozyme alone can rescue basic vascular and intestinal smooth muscle functions...