Bursts of Action Potential Waveforms Relieve G-protein Inhibition of Recombinant P/Q-type Ca2+ Channels in HEK 293 Cells

1. A variety of neurotransmitters act through G-protein-coupled receptors to decrease synaptic transmission, largely by inhibiting the voltage-gated calcium channels that trigger neurotransmitter release. However, these presynaptic calcium channels are typically inaccessible to electrophysiological characterization. We have reconstituted a part of this inhibition using recombinant P/Q-type calcium channels and M2 acetylcholine receptors in HEK 293 cells. 2. One of the most interesting 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 relieve the inhibition, increasing calcium current through G-protein-inhibited channels but not through uninhibited channels. 3. The extent of this relief increased linearly with the duration of the action potential waveforms. 4. This result provides the strongest evidence to date favouring the possibility that relief of G-protein inhibition can occur during high frequency trains of action potentials. This effect may constitute a novel form of short-term synaptic plasticity that is sensitive to action potential timing and duration.