Ultrastructural and physiological effects of the ionophore A23187 at identified frog neuromuscular junctions.

The physiological and morphological effects of the calcium ionophore A23187 (calimycin) at the frog neuromuscular junction in vitro were examined. Miniature endplate potentials were recorded intracellularly during exposure to the ionophore. Preparations fixed 15 or 30 min after adding the drug to the incubating medium, which exhibited a greatly increased miniature endplate potential frequency, showed no obvious morphological differences when compared to controls with regard to synaptic vesicle number or distribution of vesicles within the terminal. However, after 45-60 min of exposure to the ionophore, when miniature endplate potential frequency had declined almost to zero, most of the nerve endings appeared devoid of synaptic vesicles and other organelles while the plasma membrane was intact. It is suggested that the apparent depletion of vesicles from the terminal induced by the calcium ionophore is a consequence of irreversible changes at the terminal.

Synaptic vesicles and the nerve-muscle preparation in resinless sections.

Resinless sections have been used to study the fine structural organization of cellular organelles and fibrous components at synapses. Presynaptic elements of the neuromuscular junction, representing the P.N.S., and of cerebral cortical synapses, representing the C.N.S., are examined and compared. Typical ultrastructural features are apparent in presynaptic and postsynaptic components and in the surrounding muscle and neuronal tissue demonstrating the reliability and usefulness of the technique.

Retention of sarcoplasmic calcium inhibits development of the phencyclidine-restraint experimental myopathy.

The myopathy induced in the rat by the central nervous system stimulant, phencyclidine (PCP), and restraint is characterized by extensive myofibrillar sarcomere disruption in hind limb muscles and massive increases in plasma creatine kinase (CPK) activity. The effects of dantrolene sodium on this myopathy were studied to determine if modulation of calcium release from the sarcoplasmic reticulum could alter the development of the myopathy. Dantrolene prevented both the sarcomere disruption and the increase in plasma CPK activity produced in the PCP-restraint model. The inhibitory effect was not due to a decrease in the locomotor activity produced by PCP. The findings are consistent with a role for excess sarcoplasmic calcium, originating from the sarcoplasmic reticulum, in the development of this myopathy.