PMC

Cholinergic interneurons express PKCα. A: double immunostaining showed that PKCα immunoreactivity (green) was located in the cytoplasm of cholinergic interneurons (red). B and C: positive staining of PKCγ or PKCε was detected in some medium-sized striatal neurons, but not in cholinergic interneurons.

PKC activation has no effect on a potassium current (I_k) in cholinergic interneurons. A: representative traces of I_k recorded before and during application of PMA (1 μM, A1) and Go6976 (1 μM, A₂). Traces were recorded at +30 mV. B: group data showing that neither PMA (1 μM) nor Go6976 (1 μM) had an effect on I_k amplitude (evoked at +30 mV).

PKC inhibits I_A in acutely dissociated interneurons. A: representative traces of I_A recorded before and during application of PDBu (1 μM). The I_A was evoked by voltage steps from −70 to +50 mV in 20-mV increments. B: the activation curve of I_A was unchanged by application of PDBu (1 μM). C: group data showing that PDBu application reduced the saturated conductance of I_A (evoked at +70 mV; #P < 0.05).

Conventional PKC isoforms may be involved in I_A modulation. A: representative traces of I_A recorded before and during application of phorbol-12-myristate-13-acetate (PMA, 1 μM, A₁), Go6976 (1 μM, A₂) and PMA (1 μM) plus Go6976 (1 μM, A₃). Traces were recorded at +30 mV. B: group data showing that the inhibitory effects of PMA on I_A were voltage independent and that the effects of PMA were eliminated in the presence of 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (Go6967). Application of Go6976 had no effect on I_A.

PKC inhibits I_A without affecting the voltage dependent of activation and the inactivation kinetics. A: group data showing that PDBu application reduced the I_A amplitude, which was blocked by 3-[1-(dimethylaminopropyl)indol-3-yl]-4-(indol-3-yl)maleimide (GF109203X, 1 μM). Application of either chelerythrine (1 μM) or GF109203X (1 μM) had no obvious effect on I_A. The I_A was evoked at +30 mV. B: the activation curve of I_A was unchanged by application of PDBu (1 μM). C: both fast and slow time constants of I_A inactivation were not affected by PDBu application. The I_A was evoked at +30 mV (*P < 0.01).

PKC activation enhances the neuronal excitability in striatal cholinergic interneurons. A: representative traces showing the voltage responses to current pulses before and during PDBu (1 μM) application. B: representative traces showing the spike width before and during PDBu (1 μM) application. C: group data showing that PDBu application led to a decrease of the latency to the first spike and an increase of the spike number (evoked with 60-pA current, 800 ms) and spike width. (*P < 0.01).

Protein kinase C (PKC) inhibits A-type potassium current (I_A) in cholinergic interneurons. A: representative recordings showing the isolation of I_A. The I_A (A₃) was isolated by subtracting the currents evoked with depolarizing steps following a hyperpolarizing step (A₁) by the currents evoked by the same voltage steps with a prepulse of +10 mV (A₂). B: representative traces of I_A (B₃) recorded during application of phorbol-12,13-dibutyrate (PDBu, 1 μM). PDBu application suppressed I_A at each voltage step (A₃, B₃). C: protocols used to evoke voltage-gated potassium (Kv) currents and isolate I_A.

Group I metabotropic glutamate receptors (mGluRs) inhibits I_A in a subgroup of interneurons. A: representative traces of I_A recorded before and during application of (S)-3,5-dihydroxyphenylglycine (DHPG, 50 μM, A₁), DHPG (50 μM) plus (S)-α-methyl-4-carboxyphenylglycine (MCPG, 100 μM, A₂) and DHPG (50 μM) plus Go6976 (1 μM, A₃). Traces were recorded at +30 mV. B: group data showing that the inhibitory effects of DHPG on I_A were voltage independent and that the effects of DHPG were eliminated in the presence of either MCPG or Go6967.

I_A is involved in the excitatory effects of PKC. A: representative traces recorded before and during application of 4α-phorbol, 4-aminopyridine (4-AP, 1 mM) and 4-AP (1 mM) plus PDBu (1 μM). B: group data showing that 4-AP application caused an increase of the spike number (evoked with 40-pA current, 800 ms). In the presence of 4-AP, PDBu had no further effect on the spike number. C: group data showing that application of 4-AP or 4-AP + PDBu led to a similar decrease of the latency to the first spike. D: the spike width was increased during 4-AP application. Application of 4-AP + PDBu caused a similar effect on the spike width (*P < 0.01; #P < 0.05).

Synaptic inputs may not be involved in the excitatory roles of PKC. A: representative traces showing the voltage responses to current pulses before and during PMA (1 μM) application. (−)-2-Amino-5-phosphonopen phosphonopentanoic acid (APV, 50 μM), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM), and (−)-bicuculline methiodide (BIC, 30 μM) were continuously applied in bath solution to block both excitatory and inhibitory neurotransmission. B: representative traces showing the spike width before and during PMA (1 μM) application. C: group data showing that PMA application led to a decrease of the latency to the first spike and an increase of the spike number (evoked with 20- to 80-pA current, 800 ms) and spike width (*P < 0.01; #P < 0.05).