THE MECHANISM OF NORADRENERGIC ALPHA-(1) EXCITATORY MODULATION OF PONTINE RETICULAR-FORMATION NEURONS

The alpha(1) adrenergic receptor occurs in all major divisions of the CNS and is thought to play a role in all behaviors influenced by norep inephrine (NE). In the medial pontine reticular formation (mPRF), the proposed site of adrenergic enhancement of startle responses (Davis, 1 984), alpha(1) agonists excite most neurons (Gerber et al., 1990). We here report that alpha(1) excitation results from a reduction of a vol tage- and calcium-dependent potassium current, not previously recogniz ed as ligand-modulated. The calcium sensitivity is suggested by its an tagonism with Mg2+, Cd2+, Ba2+, low concentrations of tetraethylammoni um, and charybdotoxin. The voltage sensitivity of this conductance fal ls within the membrane potential range critical to action potential ge neration. Based on this voltage sensitivity, the change in repetitive firing characteristics may be predicted according to a mathematical mo del of the mPRF neuronal electrophysiology. The predicted response to a 50% decrease in the phenylephrine (PE)-sensitive conductance is simi lar to the observed responses, with respect to both the current respon se under voltage-clamp conditions and alterations of the AHP and frequ ency/current curve. In contrast, modeling a reduction of a voltage-ins ensitive leak current predicts none of these changes. Thus, the noradr energic reduction of this current depolarizes the membrane, increases the likelihood of an initial response to depolarizing input, and incre ases firing rate during sustained depolarization in a manner consisten t with an NE role as an excitatory neuromodulator of the mPRF.