A new role for P2 receptors: talking with calcium-activated potassium channels.

Purinergic fast synaptic transmission may play a very subtle role in regulating the excitability of enteric circuits. That is one of the important findings in a new paper by Ren and Galligan in the current issue of this Journal. They first provide compelling evidence that P2X(3) receptors (ionotropic purine receptors) are expressed by guinea-pig motor and interneurons and that these subtypes mediate the purinergic fast excitatory postsynaptic potential (EPSP). They also found that the P2X(3)-mediated depolarization was often followed by a hyperpolarization. This is an intriguing finding because if the purinergic fast EPSPs are also followed by a hyperpolarization, then it could play a role in truncating bursts of synaptic potentials or in shaping periodic synaptic input. The hyperpolarization is caused by calcium entry through the P2X(3) receptor which then activates a calcium-activated potassium (K(Ca)) channel. Surprisingly, the hyperpolarization was not affected by any of the standard blockers of calcium- or voltage-activated K(+) channels suggesting that a novel K(Ca) channel is present in the enteric neurons. Such a wide-spread channel could well have an important physiological role and could be an important new drug target for regulating reflex activity in the enteric nervous system.