Effects of intracellular antibodies to cGMP on responses of cortical neurons of awake cats to extracellular application of muscarinic agonists.

Intracellular injection of specific antibody to cyclic 3',5'-guanosine monophosphate (cGMP-Ab) produced substantial decreases in input resistance (Rm) selectively in neurons of the motor cortex that had responded with increased resistance to prior application of muscarinic agents. Intracellular injection of nonspecific immunoglobulins (IgG) did not produce this effect. (Some nonspecific effects on spike production occurred in cells given IgG or cGMP-Ab.) The decrease in Rm may be interpreted as being consequential to a reduction in baseline amounts of active cGMP due to binding of cGMP with the injected antibody. In cells which demonstrated a prior increase in Rm following extracellular application of the muscarinic agonist, aceclidine, or acetylcholine, injection of antibody to cGMP also resulted in suppression of the increase in Rm to subsequent applications of these muscarinic agents. Some increases in firing rate to these agents continued to be observed after injection of cGMP-Ab. The results support the hypothesis that cGMP mediates effects of muscarinic neurotransmission on the conductances of neurons of the motor cortex of awake cats. Intracellular injection of antibodies to specific cellular elements is shown to be feasible in cortical neurons of awake cats and may prove a useful adjunct to future studies of neurotransmitter mechanisms.