Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Zsombok, A. et al.

A cGMP-dependent cascade enhances an L-type-like Ca2+ current in identified snail neurons.

We studied the impact of an NO-cGMP dependent signalling pathway on the high-voltage-activated (HVA) Ca(2+) current in identified neurons of the pulmonate snail, Helix pomatia, using Ba(2+) as charge carrier. The 3',5'-cyclic guanosine monophosphate (cGMP) analogues, dibutyryl-cGMP and 8-bromo-cGMP, consistently induced a biphasic response, consisting of an increase superseded by a decline of the Ba(2+) current. The NO donor, sodium nitroprusside (SNP), modulated only in a minority of neurons the Ba(2+) current. Blockade of protein kinase activity with 1-[5-isoquinolinesulfonyl]-2 methyl piperazine (H 7), a nonselective protein kinase inhibitor, or Rp-8-pCPT-cGMP, a selective protein kinase G (PKG) inhibitor, decreased, whereas Rp-cAMP, a selective protein kinase A (PKA) inhibitor, increased the Ba(2+) current upon application of cGMP analogues or SNP. Okadaic acid or calyculin, inhibitors of protein phosphatase 1 ( PP1) and protein phosphatase 2A (PP2A), augmented the Ba(2+) current. Under these conditions, cGMP analogues or SNP had an additive-enhancing effect on the Ba(2+) current. When neurons were exposed to the nonselective phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX), cGMP analogues induced a persistent increase of the Ba(2+) current, whereas SNP induced a biphasic response. These data suggest coexistence of cGMP-PKG and cGMP-PDE pathways as well as crosstalk between cGMP and 3',5'-cyclic adenosine monophosphate (cAMP) pathways, which converge on HVA Ca channels in Helix neurons. In this model, augmentation of the Ba(2+) current through HVA Ca channels is accomplished by PKA and PKG, whereas attenuation is mediated by PDEs, which prevent activation of protein kinases via hydrolysis of cyclic nucleotides.[1]

References

A cGMP-dependent cascade enhances an L-type-like Ca2+ current in identified snail neurons. Zsombok, A., Schrofner, S., Hermann, A., Kerschbaum, H.H. Brain Res. (2005) [Pubmed]

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