Calcium influx can be enhanced at presynaptic terminals by the positive coupling of calcium channels and calcium-activated potassium channels. In their report of this finding, Xu and Slaughter describe possible ways in which potassium channel activation can lead, somewhat unexpectedly, to the amplification of synaptic transmission.

Large-conductance calcium-activated potassium (BK) channels are present at presynaptic terminals throughout the nervous system, along with voltage-dependent calcium channels, the opening of which leads to neurotransmitter release. The BK channel is activated by calcium entry into the cell and by membrane depolarization. This hyperpolarizing channel would normally be expected to provide negative feedback to transmitter release, but there is evidence to suggest that this is not always the case.

One way in which BK channels might affect transmitter release is by prolonging action potential repolarization, but studies of the action potential waveform have failed to solve the conundrum of how BK channels influence synaptic transmission. To assess the role of BK channels in the absence of action potentials, Xu and Slaughter examined release at ribbon synapses of salamander rod photoreceptors, which are non-spiking.

In dark-adapted retinal slices, BK channel blockers were found to suppress light-evoked excitatory postsynaptic currents in second-order neurons by inhibiting transmitter release from rods. Xu and Slaughter went on to show that BK and calcium channels form a positive coupled loop at the presynaptic terminal: calcium influx activates the BK channel, leading to potassium efflux, which enhances calcium channel activity. It seems that outward BK and inward calcium currents approximately balance in the normal physiological voltage range of rods, allowing amplification of synaptic transmission to occur without a change in membrane voltage. However, when the rod is further depolarized, the BK current acts as a safety brake, overwhelming other currents and hyperpolarizing the cell.

The researchers suggest that a low-affinity potassium-binding site on the extracellular side of the calcium channel enhances the calcium current, and that an increase in the concentration of local extracellular potassium could depolarize the rod terminal, thereby facilitating transmitter release. It remains to be seen whether a similar mechanism applies to some spiking neurons, in which BK channel blockers have also been found to suppress transmitter release.