| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
P2X receptors (P2X-Rs) are ATP-gated channels permeable to cations inclining Ca^<2+>. We recorded miniature excitatory postsynaptic currents (mEPSCs) under blockade of voltage-dependent Na^+ channels from second-order neurons in the nucleus tractus solitarii in vitro, a part of the brain where exogenous ATP has profound effects on autonomic outflow. Activation of presynaptic P2X-Rs with ATP or α,β-methylene ATP (α,βmATP) not only enhanced the release of glutamate, but could initiate it de novo even when voltage-dependent calcium channels (VDCCs) were completely blocked. This facilitating effect of αβmATP on the glutamate release was abolished completely by a P2X-R antagonist pyridoxalphosphate-6-azophenyl-2',4' -disulphonic acid (PPADS) and by a high, but not a low, concentration of a subtype-selective antagonist 2 > ,3 ' -O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP). Despite manifest increase in the frequency of excitatory postsynaptic events by αβmATP, the rate of the synaptic failures as evaluated by solitary tract stimulation was not significantly affected. The miniature excitatory postsynaptic potentials elicited with P2X-R agonists recorded under blockade of VDCC-dependent synaptic transmission were sufficient to trigger action potentials in the postsynaptic cell. These results show that a rise in extracellular ATP concentration promotes excitatory transmission even in the absence of presynaptic excitation, leading to a consequent activation of the autonomic networks.
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