The Role of cGMP-Dependent Signaling Pathway in Synaptic Vesicle Cycle at the Frog Motor Nerve Terminals

Abstract

The role of cGMP-dependent pathways in synaptic vesicle recycling in motor nerve endings during prolonged high-frequency stimulation was studied at frog neuromuscular junctions using electrophysiological and fluorescent methods. An increase of intracellular cGMP concentration (8-Br-cGMP or 8-pCPT-cGMP) significantly reduced the cycle time for synaptic vesicles through the enhancement of vesicular traffic rate from the recycling pool to the readily releasable pool and acceleration of fast endocytosis. Pharmacological inhibition of soluble guanylate cyclase or protein kinase G slowed down the rate of recycling as well as endocytosis of synaptic vesicles. The results suggest that cGMP-PKG-dependent pathway serves a significant function in the control of vesicular cycle in frog motor terminals.

A cGMP-dependent protein kinase (PKG) controls synaptic transmission tolerance to acute oxidative stress at the Drosophila larval neuromuscular junction

“…Acute oxidative stress was induced in larval preparations by adding 2.25 mM H 2 O 2 to the HL-3 saline. Larvae subjected to H 2 O 2 and simultaneous PKG drug treatment included one of the following agents dissolved in DMSO (all chemicals obtained from Sigma, St. Louis, MO): 40 M 8-bromo-cGMP; (a PKG activator; Ruth et al 1991), 1 M KT-5823 (a relatively selective, competitive PKG inhibitor; Grider 1993; Kase et al 1987), or 50 M Rp-8-bromo-cGMP (a more selective PKG inhibitor that irreversibly binds to the kinase; Petrov et al 2008;Wei et al 1996). These concentrations were previously shown to alter PKG activity in insect and mammalian models (Dawson-Scully et al 2007;Li et al 2007).…”

Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes ofC. elegansglutamatergic neurons

“…The acceleration effect in AWC ON endocytosis may be mediated by the large calcium influx generated by the removal of the first odor pulse, as calcium affects endocytosis in other species (Leitz and Kavalali, 2016;Neves et al, 2001;Sankaranarayanan and Ryan, 2001). Alternative or additional sources of this activity-dependent signal in AWC ON include cGMP, which can accelerate endocytosis (Petrov et al, 2008) or cytoplasmic alkalinization (Zhang et al, 2010), as the AWC ON axon becomes significantly alkalinized during odor stimulation.…”

Nitric oxide and cyclic nucleotide signal transduction modulates synaptic vesicle turnover in human model neurons

“…These experimental results suggest that the NO/cGMP signaling pathway could facilitate synaptic vesicle recycling in human neurons. A recent study demonstrates that cGMP reduces the cycle time for synaptic vesicles through the enhancement of vesicular traffic rate from the recycling pool to the readily releasable pool and accelerates fast endocytosis (Petrov et al 2008). Pre-synaptic exocytosis was followed in real time during stimulation of NT2 neurons by two NO donors, SNP and NOC-12.…”