Application of antibodies against the neural cell adhesion molecule (N-CAM) to O4-positive murine glial precursor cells in vitro results in a reduction of two distinct K+ currents measured using the whole cell patch clamp technique. Both the A-type and delayed rectifier K+ currents are reduced in amplitude within a few minutes of the application of poly- or monoclonal antibodies against N-CAM. This effect is not due to the binding of any antibody to the surface of the glial precursor cells because monoclonal antibody directed against the O4 surface antigen, or polyclonal antibodies directed against liver cell membranes (which also bind to the surface of glial precursor cells), do not affect membrane currents. Activators of protein kinase C, such as phorbol esters or diacylglycerol, also induce changes in potassium currents that appear, both in magnitude and kinetics, to be similar to those induced by antibodies against N-CAM. In contrast, activation of G proteins upregulates K+ currents. Glial precursor cells thus respond to triggering of N-CAM by altering channel properties. These observations suggest that adhesive events between neural cells can influence the intracellular ionic milieu.