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Zsombok A, Schrofner S, Hermann A, Kerschbaum HH: A cGMP-dependent cascade enhances an L-type-like Ca2+ current in identified snail neurons. Brain Res. 2005 Jan 25;1032(1-2):70-6.
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(cGMP) analogues, dibutyryl-cGMP and 8-bromo-cGMP, consistently induced a biphasic response, consisting of an increase superseded by a decline of the Ba (2+) current.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. |
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