Inhibition of N‐ and P/Q‐type Ca 2+ channels by cannabinoid receptors in single cerebrocortical nerve terminals

Since cannabinoid receptors inhibit excitatory synaptic transmission by reducing glutamate release, we have examined whether this might occur through the direct inhibition of presynaptic Ca 2+ channels. In cerebrocortical nerve terminals, activation of cannabinoid receptors with WIN55,212‐2 reduces the KCl‐evoked release of glutamate. However, this inhibition is attenuated when N‐ and P/Q‐type Ca 2+ channels are blocked. Through Ca 2+ imaging in single nerve terminals, we found that WIN55,212‐2 reduced the influx of Ca 2+ both in nerve terminals that contain N‐type Ca 2+ channels and those that contain P/Q‐type Ca 2+ channels. Thus, cannabinoid receptors modulate the two major Ca 2+ channels coupled to glutamate release in the cerebral cortex.