Enhancement of high threshold calcium currents in rat primary afferent neurons by constitutively active protein kinase C.
Protein kinase C has been implicated in the modulation of calcium channel function. However, controversy exists concerning the actions of agents such as phorbol esters or diacylglycerol (DAG) that activate endogenous PKC, with both enhancement and inhibition of Ca2+ currents described. In this article we report the effects of direct intracellular application of a constitutively active form of PKC (PKM) on whole cell calcium currents in acutely dissociated rat dorsal root ganglion neurons. PKM application significantly enhanced high threshold voltage-activated calcium currents elicited from holding potentials of -80 mV and -40 mV. The rate of current rundown in PKM-treated cells was not significantly different from controls. The enhancement observed with PKM was not due to a shift in the voltage dependence of the peak current. Synthetic PKC inhibitor peptide (PKC-I) added to recording solutions containing PKM (PKM+PKC-I) abolished the PKM-associated enhancement. The rate of current rundown was significantly increased in the presence of PKM+PKC-I, and PKC-I alone, suggesting that substantial enhancement of voltage-activated calcium currents by endogenous PKC occurred in this preparation of rat dorsal root ganglion neurons. The portions of current attributable to N-, L-, and non-N,L-type currents [determined by applying the N- and L-type calcium antagonists omega-conotoxin GVIA and nifedipine (3-10 microM)] were not affected by PKM, suggesting that both N and L current components were enhanced by PKM.(ABSTRACT TRUNCATED AT 250 WORDS)
Hall
K E
KE
Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.
Browning
M D
MD
Dudek
E M
EM
Macdonald
R L
RL
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D004056:Differential Threshold; D004553:Electric Conductivity; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015220:Calcium Channels; D011493:Protein Kinase C