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 + or - 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 + or - 65% increase in M-current (I(M)) in B cells (tau(recovery) = 153 + or - 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 microm Cd(2+) and 2.5 microm oxotremorine M (oxo-M), a muscarinic agonist, and fully blocked by zero Ca(2+), 10 microm oxo-M and 2.5 microm oxo-M plus 50 microm wortmannin, a PIP(2) 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.