Phorbol esters mimic some cholinergic actions in hippocampal pyramidal neurons

Area of Science:

• Neuroscience
• Cellular signaling

Background:

• Muscarinic receptor stimulation in the hippocampus involves inositol phospholipid breakdown.
• This breakdown generates signaling molecules that activate protein kinase C.
• Phorbol esters, known protein kinase C activators, bind specifically in the hippocampus.

Purpose of the Study:

• To investigate if protein kinase C activation is the intracellular signal for muscarinic receptor occupation.
• To examine the role of protein kinase C in mediating hippocampal muscarinic responses.

Main Methods:

• Utilized hippocampal slice preparation for direct pharmacological access to CA1 pyramidal cells.
• Compared electrophysiological effects of muscarinic agonists and phorbol esters.
• Assessed effects on calcium-activated potassium afterhyperpolarizing potential (AHP), spike discharge, and specific potassium currents (IM).

Main Results:

• Phorbol esters, like muscarinic agonists, abolished the slow calcium-activated potassium afterhyperpolarizing potential (AHP).
• Activation of protein kinase C was required to reduce the AHP.
• Phorbol esters reduced spike discharge accommodation but did not affect the muscarine-sensitive potassium current (IM) or presynaptic inhibition.

Conclusions:

• Protein kinase C activation accounts for some, but not all, electrophysiological effects of muscarinic receptor occupation in the hippocampus.
• Inositol phospholipid turnover may mediate muscarinic responses, with protein kinase C playing a partial role.