ATP receptor activation potentiates a voltage-dependent Ca channel in hippocampal neurons

Activation of a purinergic P-2 receptor by adenosine 5'-triphosphate (ATP) has previously been shown to open a non-selective cation channel with a reversal potential of approximately 0 mV. We examined the effects of P-2 receptor activation on voltage-gated ionic currents in acutely isolated CA3 pyramidal neurons from guinea pig hippocampus using the whole-cell-patch technique. Under conditions designed to isolate current through voltage-dependent Ca channels (I-Ca), ATP (50 mu M) potentiated I-Ca by 36%. This increase in I-Ca desensitized back to control levels within 4 min. In contrast to the non-selective cation channel, I-Ca, elicited from a holding potential (HP) of - 100 mV showed significant potentiation in response to ATP when depolarized to a test potential (TP) of -10 mV but showed no effect on I-Ca when the same neuron was alternately depolarized to TP = -70 mV. No change in holding current at HP = - 100 mV occurred. Tail currents were unaffected by ATP exposure suggesting that I-Ca potentiation was not due to modulation of L-type Ca channels. This potentiation was also observed either with ATP-gamma-s, the slowly hydrolyzabie ATP analog, or with ATP in the presence of alpha,beta-methylene-ADP, an ectonucleotidase inhibitor, indicating that the effects observed were not due to activation of an adenosine receptor that required ATP hydrolysis. The potentiation of I-Ca was not observed with the P-2X agonist, beta,gamma-methylene-ATP. These results suggest that ATP receptors can modulate voltage- as well as ligand-gated channels permeable to calcium and may play an important role in the dynamics of intracellular Ca2+ in these neurons.