An electrophysiological correlate of protein kinase C isozyme distribution in cultured cerebellar neurons

Abstract

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.

Chronic exposure to ammonia induces isoform‐selective alterations in the intracellular distribution and NMDA receptor‐mediated translocation of protein kinase C in cerebellar neurons in culture

“…The isoforms a, b1, c, e, d, and f have been previously detected in cerebellum and in cerebellar granule cells (Huang et al. 1988;Shimohama et al 1991;Linden et al 1992;Lin et al 1997;Yang and Kodavanti 2001). PKC c has also been detected in cerebellar granule cells (Lin et al 1997) and the low expression of this isoform in our study is in agreement with the report of Yang and Kodavanti (2001).…”

Protein phosphatase 2A inhibition induces cerebellar long-term depression and declustering of synaptic AMPA receptor

“…It should be noted that the period between the second and third postnatal week in vivo corresponds to an extensive synaptic remodeling (disappearance of functional N-methyl-Daspartate receptors and of multiple climbing fiber innervation) and changes in electrical properties resulting from alteration of voltage-dependent channel populations (45,46). The signaling cascade underlying cerebellar LTD also appears to undergo considerable maturation during this period, with neither IP 3 nor NO required in immature PCs (47,48), whereas these signals are necessary in the mature cerebellum (5). Furthermore, this period also corresponds to a drastic inversion of the relative abundance of PP-2A B ␤ and PP-2A B ␥ in the brain, two PP-2A regulatory subunits highly expressed in PCs and involved in PP-2A targeting (21).…”

Involvement of Basal Protein Kinase C and Extracellular Signal-Regulated Kinase 1/2 Activities in Constitutive Internalization of AMPA Receptors in Cerebellar Purkinje Cells

“…PKC activity enhancement induced the LTD of PF-EPSC in cultured PCs (Linden et al, 1992), but whether PKC activity enhancement increases TeTx rundown is unknown. We then examined the effect of PKC activators on TeTx rundown.…”