Calcium channels play a key role in the signal transduction between neurons in our brain. Many types of calcium channels with different biophysical and pharmacological properties have been identified. Among them, only N- and P/Q-type calcium channels have been generally thought to control transmitter release evoked by the nerve impulse. This view was challenged by the neuroscientists Ling-Gang Wu, J. Gerard G. Borst and Bert Sakmann at the Max Planck Institute for Medical Research in Heidelberg, Germany. They discovered as reported in the April 14 issue of PNAS (Vol. 95, Issue 8) that R-type calcium channels control transmitter release in presynaptic terminals of neurons that participate in localization of sound. This finding may apply to many other synapses in the brain.
Biophysical and pharmacological analysis has led to the description of six classes of calcium channels, usually referred to as L-, N-, P-, Q-, R- and T-type. Among them, only N- and P/Q-type calcium channels have been found to control transmitter release evoked by nerve impulses in all synapses examined so far. R-type calcium channels are high voltage-activated channels resistant to the known specific calcium channel blockers. Because of the lack of the specific blocker, and the difficulty in directly accessing the small presynaptic terminals (a special compartment for a neuron to communicate with the other via neurotransmitters), it could not be addressed whether R-type channels are present in the presynaptic terminals.
About three years ago, Borst and Sakmann (Journal of Physiology (London) 489, 825-840, 1995) found that the electrical signals in both the pre- and the postsynaptic sides of a single synapse between neurons in the ventral coclear nucleus and the medial nucleus of the trapezoid body can be monitored simultaneously. This technique provides a key to record and compare the electrical properties of the presynaptic calcium channels, and thus it became possible to address the question whether R-type channels are at the presynaptic terminal.
Simultaneous recordings of the presynaptic Ca2+ influx and the excitatory postsynaptic current (EPSC) evoked by a single action potential were made at single synapses. The R-type channel contributed 26% of the total Ca2+ influx during a presynaptic action potential. This Ca2+ current evoked transmitter release sufficiently large to initiate an action potential in the postsynaptic neuron. The R-type current controlled release with a lower efficacy than other types of Ca2+ currents. Neuromodulators such as the metabotropic glutamate receptor and GABAB receptor agonists inhibited the R-type current. This results suggest that modulation of R-type current provides a fine tuning of synaptic transmitter release. Because R-type channels control fast transmitter release with a lower efficacy, they may contribute preferentially to mechanisms involving slower cytoplasmic calcium signaling, such as paired-pulse facilitation post-tetanic potentiation and mobilization of synaptic vesicles. Since a significant fraction of presynaptic Ca2+ channels remain unidentified in many other central synapses, the R-type current could also contribute to evoked transmitter release in these synapses.
Journal
Proceedings of the National Academy of Sciences