Mechanism of presynaptic inhibition by neuropeptide Y at sympathetic nerve terminals

CALCIUM influx through voltage-sensitive Ca²⁺ channels is the normal physiological stimulus for the activity-dependent release of neurotransmitters at synaptic contacts. It has been postulated that presynaptic inhibition of transmitter release is due to a reduction in Ca²⁺ influx at the nerve terminal, which could result from the direct inhibition of Ca²⁺ channels. Neuropeptide Y and noradren-aline act as cotransmitters at many sympathetic synapses. Both of these substances produce presynaptic inhibition and can inhibit Ca²⁺ currents in the soma of sympathetic neurons^1-5. Here we provide direct evidence that presynaptic inhibition produced by neuropeptide Y at sympathetic nerve terminals is associated with a reduction in Ca²⁺ influx and that this is due to the selective inhibition of neuronal N-type Ca²⁺ channels.