INHIBITION OF Ca⁺⁺ TRANSPORT INTO RAT BRAIN SYNAPTOSOMES BY DIPHENYLHYDANTOIN (DPH)

¹ Departments of Neurology and Pharmacology, Washington Uiversity Medical School, St. Louis, Missouri

The effect of diphenylhydantoin (DPH) on Ca⁺⁺ uptake by isolated presynaptic nerve endings (synaptosomes) was studied. At concentrations of 0.2 mM or greater. DPH significantly inhibited Ca⁺⁺ influx into synaptosomes depolarized by 69 mM K⁺. Ca⁺⁺ transport into undepolanized synaptosomes was not inhibited until the level of DPH was equal to or greater than 0.4 mM. DPH appeared to depress the initial, rapid rate of entry of Ca⁺⁺ into depolarized synaptosomes and had no effect on the subsequent slower rate of Ca⁺⁺ influx. These results support the concept that a major pharmacological action of DPH is inhibition of Ca⁺⁺ transport into stimulated neural tissue. It is postulated that this is the mechanism by which DPH suppresses post-tetanic potentiation.