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) nucleotide receptors have been expressed by micro-injection into dissociated rat superior cervical sympathetic neurones and the effects of stimulating the expressed receptors on voltage-activated N-type Ca(2+) currents and M-type K(+) currents recorded. Both currents were reduced by stimulating all three receptors, with the following mean IC(50) 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 microM, I(Ca) 0.5 microM; P2Y(6) (agonist: UDP) - I(K(M)) 30 nM, I(Ca) 5.9 nM. Inhibition of I(K(M)) was voltage-independent and insensitive to Pertussis toxin; inhibition of I(Ca) showed both voltage-sensitive and insensitive, and Pertussis toxin-sensitive and insensitive components. It is concluded that these P2Y receptors can 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 induce both postsynaptic excitory and presynaptic inhibitory responses.
Brown
D A
DA
Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK.
Filippov
A K
AK
Barnard
E A
EA
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D006801:Humans; D009474:Neurons / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D015220:Calcium Channels; D015221:Potassium Channels; D018048:Receptors, Purinergic P2