Inhibition of potassium and calcium currents in neurones by molecularly-defined P2Y receptors

Messenger RNAs and cDNAs for individual cloned P2Y(1), P2Y2 and P2Y(6) nucl eotide receptors have been expressed by micro-injection into dissociated ra t superior cervical sympathetic neurones and the effects of stimulting the expressed receptors on voltage-activated N-type Ca2+ currents and M-type K currents recorded. Both currents were reduced by stimulating all three rec eptors, with the following mean IC50 values: P2Y(1) (agonist: ADP)- I-K(M) 6.9 nM, I-Ca 8.2 nM; P2Y(2) (agonist: UTP)- I-K(M) 1.5 mu M, I-Ca 0.5 mu M; P2Y(6) (agonist: UDP) - I-K(M) 30 nM, I-Ca 5.9 nM. Inhibition of I-K(M) wa s voltage-independent and insensitive to Pertussis toxin; inhibition of I-C a showed both voltage-sensitive and insensitive, and Pertussis toxin-sensit ive and insensitive components. Tt is concluded that these P2Y receptors ca n couple to more than one G protein and thereby modulate more than one ion channel. It is suggested that these effects on K-M and Ca-N channels may in duce both postsynaptic excitory and presynaptic inhibitory responses. (C) 2 000 Elsevier Science B.V. All rights reserved.