Homeostatic regulation of M-current modulates synaptic integration in secretomotor but not vasomotor sympathetic neurons in the bullfrog

摘要

We compared how vasomotor C neurons and secretomotor B neurons integrated identical patterns of virtual synaptic activity using dynamic clamp, perforated-patch recordings from dissociated bullfrog sympathetic ganglion cells. The synaptic template modelled one strong nicotinic synapse and nine weak synapses, each firing randomly at 5 Hz, with strength normalized to each cell. B neurons initially fired at 12 Hz, but this declined within seconds, decreasing 27% after 40 s and recovering slowly as evidenced by the threshold synaptic conductance for firing (τrecovery= 136 ± 23 s). C neurons gave an identical initial response that remained steady, declining only 6% after 40 s. The difference resulted from an activity-dependent 379 ± 65% increase in M-current (IM) in B cells (τrecovery= 153 ± 22 s), which was absent in C cells. In addition, action potential afterhyperpolarizations were 2-fold longer in B cells, but this did not produce the differential response to synaptic stimulation. Activity-dependent increases in IM were sensitive to 100 μm Cd²⁺ and 2.5 μm oxotremorine M (oxo-M), a muscarinic agonist, and fully blocked by zero Ca²⁺, 10 μm oxo-M and 2.5 μm oxo-M plus 50 μm wortmannin, a PIP2 synthesis inhibitor. A leftward shift in voltage-dependent activation could not fully account for the IM increase. Firing at 0.5 Hz was sufficient to modulate IM. Opposing influences of activity and muscarinic excitation thus produce homeostatic IM regulation, to stabilize excitability and postsynaptic output in secretomotor sympathetic neurons. Absence of this regulation in vasomotor neurons suggests a different integrative function, where synaptic gain increases in proportion to presynaptic activity.