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

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 (tau(recovery) = 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 (I-M) in B cells (tau(recovery) = 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 I-M were sensitive to 100 mu m Cd2+ and 2.5 mu m oxotremorine M (oxo-M), a muscarinic agonist, and fully blocked by zero Ca2+, 10 mu m oxo-M and 2.5 mu m oxo-M plus 50 mu m wortmannin, a PIP2 synthesis inhibitor. A leftward shift in voltage-dependent activation could not fully account for the I-M increase. Firing at 0.5 Hz was sufficient to modulate I-M. Opposing influences of activity and muscarinic excitation thus produce homeostatic I-M 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.