Journal of Neuroscience, Vol 12, 3601-3608, Copyright © 1992 by Society for Neuroscience
An electrophysiological correlate of protein kinase C isozyme distribution in cultured cerebellar neurons
DJ Linden, M Smeyne, SC Sun and JA Connor
Department of Neurosciences, Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
Protein kinase C (PKC) is a family of at least seven closely related
molecules (isozymes) that vary in terms of their requirements for
activation and their distribution among cells of the brain. A striking
example of this differential distribution is seen in the cerebellum, where
Purkinje cells express PKC-I, an isozyme that is strongly activated by both
phorbol ester (PE), and low doses of cis-unsaturated fatty acid (c-UFA),
while granule cells predominantly express PKC-II, an isozyme that is
strongly activated by PE but not c-UFA. Both Purkinje and granule cells
have large, easily recorded voltage-gated K currents. These currents are
attenuated by PKC activators in several other varieties of neuron. We
hypothesized that the effects of these two PKC activators would be
predicted by the distribution of the relevant PKC isozyme, and that the
delayed outward rectifier current, IK, would be attenuated by both PE and
c-UFA in Purkinje cells, but only by PE in granule cells. This hypothesis
was confirmed in perforated-patch recordings. The attenuation produced by
both activators could be blocked by application of a specific PKC
inhibitor, RO-31-8220, and could not be mimicked by inert forms of PE or
c-UFA. To our knowledge, this study represents the first report of an
electrophysiological correlate of PKC isozyme distribution.