Inhibitory adenosine A1-receptors on rat locus coeruleus neurones. An intracellular electrophysiological study

Intracellular recordings were performed in a pontine slice preparation of the rat brain containing the locus coeruleus (LC). Adenosine (100, 300 mumol/l) and its structural analogues, namely (-)-N6-(R-phenylisopropyl)-adenosine (R-PIA; 3-30 mumol/l) and S-PIA (10, 30 mumol/l), as well as 5'-N-ethylcarboxamido-adenosine (NECA; 3-30 mumol/l) inhibited the firing rate of spontaneous action potentials and produced hyperpolarization; their rank order of potency was R-PIA congruent to NECA greater than S-PIA greater than adenosine. When applied by superfusion, all agonists strongly desensitized the LC cells; the hyperpolarization never surmounted 6 mV. Upon pressure ejection of adenosine 10 mmol/l from a micropipette positioned close to an LC neurone, the membrane potential was raised by 14 mV and the apparent input resistance decreased by 20%. When the membrane potential was hyperpolarized by current injection to a similar extent as adenosine did, the fall in input resistance was only 7%. The adenosine uptake inhibitor S-(p-nitrobenzyl)-6-thioguanosine (NBTG) 30 mumol/l decreased the frequency of action potentials alone; on simultaneous bath-application with adenosine 300 mumol/l it potentiated the hyperpolarization caused by the purine derivative. 8-Cyclopentyl-1,3-dipropylxanthine (CPDPX) 0.1 mumol/l had no effect on its own, but it antagonized both R-PIA 30 mumol/l and NBTG 30 mumol/l. A higher concentration of CPDPX (1 mumol/l) facilitated the spontaneous firing. In conclusion, both exogenous and endogenous adenosine activates somatic and/or dendritic A1-receptors of LC neurones leading to an enhancement of potassium conductance and thereby to a decreased firing rate and a hyperpolarization.