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

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Abstract

Messenger RNAs and cDNAs for individual cloned P2Y1, P2Y2 and P2Y6 nucleotide receptors have been expressed by micro-injection into dissociated rat 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 receptors, with the following mean IC50 values: P2Y1 (agonist: ADP) – IK(M) 6.9 nM, ICa 8.2 nM; P2Y2 (agonist: UTP) – IK(M) 1.5 μM, ICa 0.5 μM; P2Y6 (agonist: UDP) – IK(M) 30 nM, ICa 5.9 nM. Inhibition of IK(M) was voltage-independent and insensitive to Pertussis toxin; inhibition of ICa 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 KM and CaN channels may induce both postsynaptic excitory and presynaptic inhibitory responses.

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Acknowledgements

This work was supported by grants from the Wellcome Trust.

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