Nitric oxide/cGMP/PKG signaling pathway activated by M₁-type muscarinic acetylcholine receptor cascade inhibits Na⁺-activated K⁺currents in Kenyon cells

Abstract

activity in Kenyon cells of crickets (Gryllus bimaculatus). We found that two different NO donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl-DL-penicillamine(SNAP), strongly suppressed K Na channel currents. Additionally, this inhibitory effect of GSNO on K Na channel activity was diminished by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), and KT5823, an inhibitor of protein kinase G (PKG). Next, we analyzed the role of ACh in the NO signaling cascade. ACh strongly suppressed K Na channel currents, similar to NO donors. Furthermore, this inhibitory effect of ACh was blocked by pirenzepine, an M 1 muscarinic ACh receptor antagonist, but not by 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) and mecamylamine, an M 3 muscarinic ACh receptor antagonist and a nicotinic ACh receptor antagonist, respectively. The ACh-induced inhibition of K Na channel currents was also diminished by the PLC inhibitor U73122 and the calmodulin antagonist W-7. Finally, we found that ACh inhibition was blocked by the nitric oxide synthase (NOS) inhibitor N G -nitro-L-arginine methyl ester (L-NAME). These results suggested that the ACh signaling cascade promotes NO production by activating NOS and NO inhibits K Na channel currents via the sGC/cGMP/PKG signaling cascade in Kenyon cells.

Nitric oxide augments single persistent Na+channel currents via the cGMP/PKG signaling pathway in Kenyon cells isolated from cricket mushroom bodies

“…In the cricket G. bimaculatus, NOS expression is highly observed in large Kenyon cells and not in small Kenyon cells; a high level of expression of NOS mRNA has been observed in the outer layer of the mushroom body but not in the inner layer of the mushroom body in the cricket (Takahashi et al 2009). Hasebe and Yoshino (2016) showed that the inhibitory action of acetylcholine (ACh) on Na ϩactivated K ϩ channel in the cricket G. bimaculatus is blocked by W-7, a Ca 2ϩ /calmodulin (CaM) inhibitor, and the NOS inhibitor L-NAME, suggesting that an increase in intracellular Ca 2ϩ is essential for activation of NOS. Based on these observations and our present findings, it seems that large Kenyon cells use their self-produced NO as an intrinsic modulator.…”

“…In these cells, the voltage-dependent Ca 2ϩ channel currents are augmented by NO/cGMP/PKG signaling, whereas the Na ϩ -activated K ϩ currents (Aoki et al 2008) are inhibited by NO/ cGMP/PKG signaling (Hasebe and Yoshino 2016). Hasebe and Yoshino (2016) suggested that NO-mediated inhibition of Na ϩ -activated K ϩ channels induces long-lasting depolarization by blocking tight coupling between Na ϩ channels and Na ϩ -activated K ϩ channels (Takahashi and Yoshino 2015).…”

Phosphodiesterase Inhibitors for Alzheimer’s Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale

“…Particulate GC-A and GC-B produce cGMP proximal to the plasma membrane [67,68]. cGMP activates protein kinase G (PKG) [64,65].…”

“…Regarding cGMP signaling, nitric oxide synthases (NOS) produce nitric oxide (NO).NO activates soluble guanylyl cyclase (sGC) in the cytoplasm. sGC produces cytoplasmic cGMP [ 64, 65 ]. In addition, Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) activate particulate, plasma-membrane localized, receptor guanylyl cyclase-A (GC-A) [ 66 ], and C-type natriuretic peptide (CNP) activates the particulate guanylyl cyclase B (GC-B) [ 67 ].…”

Signaling Pathways for Long-Term Memory Formation in the Cricket

“…The new model illustrates the simplest of all the signaling pathways that account for the results summarized in Table 1 , which describes the outcomes of co-injection experiments. The following documented findings in several insects are incorporated in this model: (1) in vitro alpha-bungarotoxin (BGT)-sensitive nicotinic acetylcholine receptors (nAChRs) are able to trigger NO synthesis in Kenyon cells of insects ( Bicker et al, 1996 ; Zayas et al, 2002 ), (2) NO production by NO synthase is stimulated by Ca 2+ /CaM in Drosophila ( Regulski and Tully, 1995 ), (3) in vitro muscarinic acetylcholine receptors (mAChR) activate CaM by calcium release from the endoplasmic reticulum (ER) via PLC/IP 3 signaling ( Hasebe and Yoshino, 2016 ), (4) calcium release via ryanodine receptors (RyRs) on the ER induces LTM in crickets ( Sugimachi et al, 2016 ), (5) AC is activated by either the G-protein coupled receptor or Ca 2+ /CaM in Drosophila ( Livingstone et al, 1984 ) and (6) PKA activates CREB which leads to LTM formation in Drosophila ( Yin et al, 1995 ).…”