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

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) – I_K(M) 6.9 nM, I_Ca 8.2 nM; P2Y₂ (agonist: UTP) – I_K(M) 1.5 μM, I_Ca 0.5 μM; P2Y₆ (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.