Propylparaben reduces the excitability of hippocampal neurons by blocking sodium channels |
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| Institution: | 1. Department of Physiology & Pharmacology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;2. Department of Anatomical Sciences, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;3. Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;4. Department of Toxicology and Pharmacology, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;5. Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran;1. Center for Structural and Functional Neuroscience, Center for Environmental Health Sciences, Department of Biomedical & Pharmaceutical Sciences, College of Health Professions and Biomedical Sciences, The University of Montana, Missoula, MT 59812, United States;2. Business Planning Department, Kyowa Hakko Kirin Korea Co., Ltd., Seoul, Republic of Korea;1. Departamento de Farmacobiología, Cinvestav, Sede Sur, México;2. División de Estudios de Posgrado, Facultad de Ciencias Médicas y Biológicas “Dr. Ignacio Chávez”, Universidad Michoacana de San Nicolás de Hidalgo, México;1. Institut National de Recherche et de Sécurité, Rue du Morvan, F-54519 Vandoeuvre-les-Nancy, France;2. Service O.R.L. et Chirurgie Cervico-faciale CHU-Hôpital Central, Nancy, F-54000, France;3. Université de Lorraine, CRM2, UMR 7036, Vandoeuvre-les-Nancy, F-54506, France;4. CNRS, CRM2, UMR 7036, Vandoeuvre-les-Nancy, F-54506, France |
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| Abstract: | 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. |
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| Keywords: | Propylparaben Neuronal excitability Sodium currents CA1 pyramidal cells |
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