Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.12 (PKG)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

C-type dorsal root ganglion (DRG) neurons express three types of Na+ currents: fast TTX-sensitive, slow TTX-resistant, and persistent TTX-resistant Na+ currents. The nitric oxide (NO) donors papa-NONOate and S-nitroso-N-acetyl-DL-penicillamine inhibit all three types of Na+ currents. The NO scavenger hemoglobin abolished the effects of papa-NONOate on Na+ currents, indicating that NO or NO-related species inhibit these Na+ currents. NO donor inhibition of all three types of Na+ currents was reversed by washout. Incubation of neurons with 8-bromo cGMP, a membrane-permeable analogue of cGMP, and cG-PKI, an inhibitor of cGMP-dependent protein kinase, had no effect on papa-NONOate-mediated Na+ current block, demonstrating that Na+ current inhibition is independent of cGMP. Alkylation of free thiols with N-ethylmaleimide prevented the actions of papa-NONOate, suggesting that NO, or a related reactive nitrogen species, modifies sulfhydryl groups on Na+ channels or a closely associated protein. Papa-NONOate-mediated block of Na+ currents is not due to a hyperpolarizing shift in steady state voltage-dependent inactivation. The absence of NO-mediated enhancement of slow inactivation in fast and slow Na+ channels indicates that NO does not inhibit fast and slow Na+ channels by facilitating the transition to a slow inactivated state. These results demonstrate that inhibition of Na+ currents is not due to the modulation of fast and slow sodium channel inactivation. Taken together, these results show that NO or NO-related products modify the sulfhydryl groups on Na+ channels and inhibit Na+ currents by blocking the channel conductance.
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PMID:Nitric oxide blocks fast, slow, and persistent Na+ channels in C-type DRG neurons by S-nitrosylation. 1182 45

Evaluation of: Noorman M, Hakim S, Kessler E et al. Remodeling of the cardiac sodium channel, connexin43, and plakoglobin at the intercalated disk in patients with arrhythmogenic cardiomyopathy. Heart Rhythm 10(3), 412-419 (2013). Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease characterized by a progressive replacement of the ventricular myocardium with adipose and fibrous tissue. This disease is often associated with mutations in genes encoding desmosomal proteins in the majority of patients. Based on results obtained from recent experimental models, a disturbed distribution of gap junction proteins and cardiac sodium channels may also be observed in AC phenotypes, secondary to desmosomal dysfunction. The study from Noorman et al. examined heart sections from patients diagnosed with AC and performed immunohistochemical analyses of N-cadherin, PKP2, PKG, Cx43 and the cardiac sodium channel NaV1.5. Altered expression/distribution of Cx43, PKG and NaV1.5 was found in most cases of patients with AC. The altered expression and/or distribution of NaV1.5 channels in AC hearts may play a mechanistic role in the arrhythmias leading to sudden cardiac death in AC patients. Thus, NaV1.5 should be considered as a supplemental element in the evaluation of risk stratification and management strategies. However, additional experiments are required to clearly understand the mechanisms leading to AC phenotypes.
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PMID:NaV1.5 and interacting proteins in human arrhythmogenic cardiomyopathy. 2317 89