Protein kinase C pathways modulate respiratory pattern generation in the cat.

1. The significance of protein kinase C (PKC) in respiratory pattern generation was investigated in forty-three expiratory neurones of anaesthetized cats. 2. Intracellular injection of R-2,6-diamino-N-([1-(oxotridecyl)-2-piperidinyl]-methyl)-hexana mide dihydrochloride reversibly hyperpolarized twenty-six neurones. Respiratory drive potentials decreased to 92% of control, and action potential discharges were reduced. Neuronal input resistance (Rin) decreased during inspiration and increased during expiration. 3. Voltage clamp revealed that blockade of PKC induced an increase of inhibitory drive currents and a decrease of excitatory drive currents in sixteen neurones. The amplitude of respiratory drive currents was decreased to 91% of control. The slope of synaptic inward currents during postinspiration was reduced. 4. After blockade of K+ conductances by TEA, additional blockade of PKC caused a hyperpolarization during postinspiration and expiration, but depolarization during inspiration in fourteen neurones. The respiratory drive currents were reduced to 61% of control. Respiratory drive potentials decreased to 72% of control, leading to reduced spontaneous discharge. Rin was increased throughout the respiratory cycle. 5. Stimulus-evoked postsynaptic currents and potentials decreased after blockade of PKC with and without TEA. 6. The results indicate that PKC is endogenously active in expiratory neurones, modulating their excitability in three different ways: (a) it downregulates persistent K+ currents, (b) it upregulates Cl(-)-mediated inhibitory postsynaptic currents (IPSCs), and (c) it upregulates excitatory postsynaptic currents (EPSCs).