Propylparaben reduces the excitability of hippocampal neurons by blocking sodium channels.
Propylparaben (PPB) is an antimicrobial preservative widely used in food, cosmetics, and pharmaceutics. Virtual screening methodologies predicted anticonvulsant activity of PPB that was confirmed in vivo. Thus, we explored the effects of PPB on the excitability of hippocampal neurons by using standard patch clamp techniques. Bath perfusion of PPB reduced the fast-inactivating sodium current (INa) amplitude, causing a hyperpolarizing shift in the inactivation curve of the INa,and markedly delayed the sodium channel recovery from the inactivation state. Also, PPB effectively suppressed the riluzole-sensitive, persistent sodium current (INaP). PPB perfusion also modified the action potential kinetics, and higher concentrations of PPB suppressed the spike activity. Nevertheless, the modulatory effects of PPB did not occur when PPB was internally applied by whole-cell dialysis. These results indicate that PPB reduces the excitability of CA1 pyramidal neurons by modulating voltage-dependent sodium channels. The mechanistic basis of this effect is a marked delay in the recovery from inactivation state of the voltage-sensitive sodium channels. Our results indicate that similar to local anesthetics and anticonvulsant drugs that act on sodium channels, PPB acts in a use-dependent manner.
Departamento de Farmacobiología, Cinvestav Sede Sur, México City, Mexico.
Leonardo
L
Lara-Valderrábano
Departamento de Farmacobiología, Cinvestav Sede Sur, México City, Mexico.
Luisa
L
Rocha
Departamento de Farmacobiología, Cinvestav Sede Sur, México City, Mexico. Electronic address: ejgalvan@cinvestav.mx.
Emilio J
EJ
Galván
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010226:Parabens / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D018696:Neuroprotective Agents; D010226:Parabens; D011310:Preservatives, Pharmaceutical; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D019782:Riluzole; C006068:propylparaben
CA1 pyramidal cells; Neuronal excitability; Propylparaben; Sodium currents