PT  - JOURNAL ARTICLE
AU  - Doerner, D
AU  - Pitler, TA
AU  - Alger, BE
TI  - Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons
AID  - 10.1523/JNEUROSCI.08-11-04069.1988
DP  - 1988 Nov 01
TA  - The Journal of Neuroscience
PG  - 4069--4078
VI  - 8
IP  - 11
4099  - http://www.jneurosci.org/content/8/11/4069.short
4100  - http://www.jneurosci.org/content/8/11/4069.full
SO  - J. Neurosci.1988 Nov 01; 8
AB  - Whole-cell voltage-clamp techniques were used to study the effects of the protein kinase C (PKC) activators phorbol esters and OAG on Ca and K currents in differentiated neurons acutely dissociated from adult hippocampus and in tissue-cultured neurons from fetal hippocampus. PKC activators had selective depressant effects on K currents, with persistent currents (IK and IK-Ca) being reduced and transient current (IA) being unaffected. In both cell types we recorded both high-voltage- activated, noninactivating (L-type) and high-voltage-activated, rapidly inactivating (N-type) Ca current. A low-voltage-activated, rapidly inactivating (T-type) Ca current was also recorded in tissue-cultured neurons but not in acutely dissociated neurons. PKC activators markedly reduced N-type current with less effect on L-type and no effect on T- type Ca current. Effects of PKC activators could be reversed with washing or with application of PKC inhibitors H-7 or polymyxin-B, an effect that could not be attributed to inhibition of cAMP-dependent protein kinase. The Ca/calmodulin inhibitor calmidazolium was ineffective in reversing the actions of PKC activators. Using whole- cell voltage-clamp techniques, we have demonstrated that hippocampal neurons possess 3 distinguishable components of calcium current. Distinct K currents were also observed. Our data strongly support the hypothesis that both Ca and K currents are selectively regulated by PKC and that these effects occur directly on the postsynaptic neuron.