Guanidine Hydrochloride

Guanidine hydrochloride acts presynaptically by inhibiting voltage-gated potassium channels, leading to enhanced release of acetylcholine at the neuromuscular junction. This stimulatory effect underlies its therapeutic use for Lambert-Eaton myasthenic syndrome and botulism. The mechanism of Kv channel inhibition by guanidine was investigated using the Shaker potassium channel expressed in Xenopus oocytes. Several possible mechanisms were examined, including charge screening, disruption of protein-lipid interfaces, direct interaction with voltage sensors, and pore binding. Electrophysiological recordings demonstrated that guanidine, methyl guanidine and dimethyl guanidine inhibit the Shaker channel by binding within the intracellular pore. The inhibitors perturb a hydrophobic subunit interface to stabilize a closed state of the channel, rather than acting through charge screening or disruption of protein-lipid interactions.
This mechanism provides a structural foundation for understanding how guanidine enhances neurotransmitter release and offers a basis for designing guanidine analogs with improved therapeutic indices for neuromuscular diseases.

Fig. 1 Effect of Guanidine compounds on movement of the Shaker voltage sensors. (Kalia J, Swartz K J. 2011)

Guanidine hydrochloride at a low concentration of 2 mM was found to expand the channels of apo-soybean seed ferritin at pH 7.0 without disassembling the protein cage. This channel expansion promoted the encapsulation of rutin molecules into the ferritin cavity. Upon removal of guanidine hydrochloride, the rutin-loaded ferritin nanoparticles were homogeneously distributed with a shell-like morphology and an outer diameter of 12 nm, achieving an encapsulation ratio of 10.1 percent.
The approach enables nano-encapsulation of food bioactive molecules within the ferritin cage under benign conditions without extreme pH changes, which is beneficial for the stability and bioactivity of pH-sensitive molecules in food delivery applications.

Fig. 2 Guanidine hydrochloride-induced channel expansion of apoferritin and the particle size distribution of the resulting nanoparticles. (Yang R.; et al. 2018)