THE ACTION OF CALCIUM AND OF LOCAL ANESTHETICS ON NERVE CELLS, AND THEIR INTERACTION DURING EXCITATION

¹ Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois

The intracellular activity of neurons of isolated frog spinal ganglia was recorded with glass microelectrodes. The cells were excited orthodromically and by direct stimulation through the same microelectrode used for recording.

Excess calcium enhanced the amplitude of orthodromic spikes, while the changes in amplitude of directly elicited spikes were inconsistent. Most frequently the rates of rise and fall decreased in high calcium; however, an increase or no change was also seen. Both types of action potential were depressed by low calcium. The membrane resting potential was either unchanged or slightly increased (2 to 3 mV) by a 5-fold increase in the calcium concentration.

When the cells were activated orthodromically, local anesthetics (procaine or lidocaine 0.005 to 0.01%) produced a block between nonmyelinated axon segment and soma. The same local anesthetic doses decreased the amplitude of directly elicited spikes during the first 20 minutes; thereafter, the amplitude maintained a stable value for several hours.

A 5- to 10-fold increase in calcium during perfusion with local anesthetics prolonged the blocking time of orthodromic spikes and restored directly elicited spikes to a degree depending on the local anesthetic concentration.

The excitability changes of the cells were studied by determining the strength-duration curve. The rheobase was higher in procaine and in excess calcium than in normal saline; a further increase occurred when procaine was applied to the preparation in the presence of high calcium.

Hyperpolarization immediately preceding cell activation was more effective in enhancing the spike amplitude after the depressant action of the local anesthetic than in normal saline.

The data are discussed in the light of present theories on the role of calcium in excitation and on the mechanism of action of local anesthetics. Our results suggest that calcium and local anesthetics act at different membrane sites.

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