Modulation of high-threshold Ca current and spontaneous postsynaptic transient currents by phorbol 12,13-diacetate, 1-(5-isoquinolinesulfonyl)-2-methyl piperazine (H-7), and monosialoganglioside (GM1) in CA1 pyramidal neurons of rat hippocampus in vitro.
Phorbol esters, which activate protein kinase C (PKC), enhance synaptic transmission in the CA1 subfield of hippocampus, both in situ and in vitro. The increase in synaptic transmission could be the consequence of enhanced Ca influx into nerve terminals, and perhaps a more general increase in voltage-dependent Ca currents. The effects of phorbol 12,13-diacetate (PDAc) on the high-voltage activated (HVA) Ca currents, as well as spontaneous transient currents were therefore investigated by intracellular recording in hippocampal slices. PDAc selectively augmented, by 45% +/- 10%, the early peak of the HVA Ca current (but not its sustained component), and also spontaneous inhibitory postsynaptic currents. The inactive phorbol ester, 4 alpha-PDAc, had no comparable effects. The actions of PDAc were reversible on prolonged washing, and they were antagonized by the PKC inhibitors (1-(5-isoquinolinesulfonyl)-2-methyl piperazine (H-7) and monosialoganglioside (GM1). In addition, GM1, which also activates the Ca/calmodulin-dependent kinase, enhanced spontaneous excitatory postsynaptic currents, while inhibiting the IPSCs. It is concluded that activation of PKC increases HVA (probably N-type) Ca current and facilitates ongoing GABAergic IPSCs.
Physiology Research Department, McGill University, Montréal, Québec, Canada.
N
N
Agopyan
P
P
Miu
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K
Krnjević
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010703:Phorbol Esters / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D015220:Calcium Channels; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; C008874:phorbol-12,13-diacetate; D005677:G(M1) Ganglioside; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D002118:Calcium