BURSTS OF ACTION-POTENTIAL WAVE-FORMS RELIEVE G-PROTEIN INHIBITION OFRECOMBINANT P Q-TYPE CA2+ CHANNELS IN HEK-293 CELLS/

1. A variety of neurotransmitters act through G-protein-coupled recept ors to decrease synaptic transmission, largely by inhibiting the volta ge-gated calcium channels that trigger neurotransmitter release. Howev er, these presynaptic calcium channels are typically inaccessible to e lectrophysiological characterization. We have reconstituted a part of this inhibition using recombinant P/Q-type calcium channels and M(2) a cetylcholine receptors in HEK 293 cells. 2. One of the most interestin g features of G-protein inhibition of calcium channels is that strong step depolarization transiently relieves the inhibition. We have found that short bursts of action potential voltage waveforms can also reli eve the inhibition, increasing calcium current through G-protein-inhib ited channels but not through uninhibited channels. 3. The extent of t his relief increased linearly with the duration of the action potentia l waveforms. 4. This result provides the strongest evidence to date fa vouring the possibility that relief of G-protein inhibition can occur during high frequency trains of action potentials. This effect may con stitute a novel form of short-term synaptic plasticity that is sensiti ve to action potential timing and duration.