Role of the NP-cGMP-PKG pathway in dendroaspis natriuretic peptide-induced inhibition of delayed rectifier potassium current
Year: 2010
Type: article
Abstract: AIM: To investigate the role of the natriuretic peptide (NP)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway in dendroaspis natriuretic peptide (DNP)-induced inhibition of delayed rectifier potassium currents (I(subscript K(V))) in gastric antral circular smooth muscle of guinea pigs and to explore potential mechanisms involved. METHODS: The whole cell patch-clamp technique was used to record delayed rectifier potassium current (I(subscript K(V))) and to investigate the role of the NP-cGMP-PKG pathway in DNP-induced inhibition of I(subscript K(V)) in gastric myocytes isolated by collagenase digestion. RESULTS: DNP significantly inhibited I(subscript K(V)) in a concentration-dependent manner. DNP at concentrations of 0.01, 0.1 and 1 μmol/L (at 60 mV) decreased I(subscript K(V)) to 83.5%±2.1%, 71.8%±2.3% and 63.8±2.2% of control level, respectively. LY83583 (0.1 μmol/L), a guanylate cyclase inhibitor, significantly impaired DNP (1 μmol/L)-induced inhibition of I(subscript K(V)) (63.8%±2.2% vs 76.8%±2.3%) at 60 mV. Moreover, DNP-induced inhibition of I(subscript K(V)) was potentiated by zaparinast (1μmol/L), a cGMP-sensitive phosphoesterase inhibitor (63.8%±2.2% vs 56.8%±2.1%). DNP-induced inhibition of I(subscript K(V)) was completely blocked by KT5823, an inhibitor of cGMP-dependent PKG, but not affected by KT-5720, a protein kinase A (PKA)-specific inhibitor. CONCLUSION: DNP inhibits I(subscript K(V)) in a NPcGMP-PKG pathway-dependent and cAMP/PKA pathway-independent manner. I(subscript K(V)) may play a critical role in regulating resting membrane potential in the gastric antral circular myocytes of guinea pigs.
Authors: Zheng-Xu Cai, Sheng Li, Chun-Yu Cai, Cheng-Long Qu, Qing-Hui Qi, Hui-Shu Guo
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W122831329