Atp receptor activation potentiates a voltage-dependent ca channel in hippocampal neurons (original) (raw)

Activation of a purinergic P, 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 P2 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,,), ATP (50 PM) potentiated I,, by 36%. This increase in &-, desensitized back to control levels within 4 min. In contrast to the non-selective cation channel, I,, 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,, 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,, p otentiation was not due to modulation of L-type Ca channels. This potentiation was also observed either with ATP-y-s. the slowly hydrolyzable ATP analog, or with ATP in the presence of cr,P-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,, was not observed with the P2x agonist, P.y-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,