Faculty Bibliography

The electrophysiological properties of guinea-pig inferior olivary (I.O.) cells have been studied in an in vitro brain stem slice preparation. 1. Intracellular recordings from 185 neurones in this nucleus reveal that antidromic, orthodromic or direct stimulation generates action potentials consisting of a fast spike followed by an after-depolarizing potential (ADP). The ADP had an amplitude of 49 +/- 8 mV (mean +/- S.D.) and a duration which varied over a wide range with the level of depolarization. This ADP is followed by an after-hyperpolarizing potential (AHP) having an amplitude of 12 +/- 3 mV (mean +/- S.D.) from rest and lasting up to 250 msec. The AHP shows a rebound depolarization wave. 2. Synaptic activation may be obtained by peri-olivary stimulation with a bipolar electrode located in the immediate vicinity of the I.O. nucleus. These potentials are a mixture of depolarizing and hyperpolarizing synaptic events which can be reversed by direct membrane polarization. 3. Addition of tetrodotoxin (TTX) to the bath, or removal of extracellular Na, abolishes the fast initial action potential but does not modify the ADP or the AHP. Blockage of Ca conductance by Co, Mn, Cd or D600, or replacement of Ca by Mg, abolishes the ADP--AHP sequence. 4. Hyperpolarization of the neurone uncovers a low-threshold Ca conductance which is inactivated at rest and has similar pharmacological properties to the ADP. This low-threshold spike plays a central role in the rebound potential following the AHP. 5. Simultaneous impalement of I.O. neurone pairs demonstrated the presence of electrotonic coupling between neurones, which is especially prominent in the medial accessory olive.

A voltage clamp study has been performed in the presynaptic terminal of the squid stellate ganglion. After blockage of the voltage-dependent sodium and potassium conductances, an inward calcium current is demonstrated. Given a step-depolarization pulse, this voltage- and time-dependent conductance has an S-shaped onset. At the 'break' of the voltage step, a rapid tail current is observed. From these results a kinetic model is generated which accounts for the experimental results and predicts for the time course and amplitude a possible calcium entry during presynaptic action potentials.

The relationship between calcium current and transmitter release was studied in squid giant synapse. It was found that the voltage-dependent calcium current triggers the release of synaptic transmitter in direct proportion to its magnitude and duration. Transmitter release occurs with a delay of approximately 200 mus after the influx of calcium. A model is presented which describes these relations formally.