Intracellular studies on the role of calcium in regulating the activity and reactivity of locus coeruleus neurons in vivo.

EGTA, a specific calcium chelator, was injected intracellularly into presumed noradrenergic neurons of the rat locus coeruleus to evaluate the importance of calcium-dependent processes in regulating the activity and reactivity of these cells in vivo. The amplitude and duration of postactivation after hyperpolarizations induced by intracellular depolarizing pulses were markedly reduced in EGTA-treated cells; this change was associated with: (1) an increase in spontaneous firing rate; (2) a reduction in postactivation inhibition of firing; and (3) an increased reactivity to sensory stimulation. In control cells the reversal potential of the after hyperpolarization was at least 25 mV below 'resting' levels, indicating that an increase in potassium conductance was probably involved. Since EGTA virtually abolished the after hyperpolarization, the data are consistent with the concept that the after hyperpolarization is mediated by a calcium-activated potassium current. A calcium-dependent release of norepinephrine acting via alpha 2-adrenoceptors might also contribute to the after hyperpolarization. In conclusion, the influx of calcium into locus coeruleus neurons appears to serve a negative feedback function in the regulation of both spontaneous activity and reactivity to orthodromic stimulation.