| First Author | Lin KH | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 4 | Pages | 1261-72 |
| PubMed ID | 22279211 | Mgi Jnum | J:180584 |
| Mgi Id | MGI:5306676 | Doi | 10.1523/JNEUROSCI.3838-11.2012 |
| Citation | Lin KH, et al. (2012) Similar intracellular Ca2+ requirements for inactivation and facilitation of voltage-gated Ca2+ channels in a glutamatergic Mammalian nerve terminal. J Neurosci 32(4):1261-72 |
| abstractText | Voltage-gated Ca(2+) channels (VGCCs) of the P/Q-type, which are expressed at a majority of mammalian nerve terminals, show two types of Ca(2+)-dependent feedback regulation-inactivation (CDI) and facilitation (CDF). Because of the nonlinear relationship between Ca(2+) influx and transmitter release, CDI and CDF are powerful regulators of synaptic strength. To what extent VGCCs inactivate or facilitate during spike trains depends on the dynamics of free Ca(2+) ([Ca(2+)](i)) and the Ca(2+) sensitivity of CDI and CDF, which has not been determined in nerve terminals. In this report, we took advantage of the large size of a rat auditory glutamatergic synapse-the calyx of Held-and combined voltage-clamp recordings of presynaptic Ca(2+) currents (I(Ca(V))) with UV-light flash-induced Ca(2+) uncaging and presynaptic Ca(2+) imaging to study the Ca(2+) requirements for CDI and CDF. We find that nearly half of the presynaptic VGCCs inactivate during 100 ms voltage steps and require several seconds to recover. This inactivation is caused neither by depletion of Ca(2+) ions from the synaptic cleft nor by metabotropic feedback inhibition, because it is resistant to blockade of metabotropic and ionotropic glutamate receptors. Facilitation of I(Ca(V)) induced by repetitive depolarizations or preconditioning voltage steps decays within tens of milliseconds. Since Ca(2+) buffers only weakly affect CDI and CDF, we conclude that the Ca(2+) sensors are closely associated with the channel. CDI and CDF can be induced by intracellular photo release of Ca(2+) resulting in [Ca(2+)](i) elevations in the low micromolar range, implying a surprisingly high affinity of the Ca(2+) sensors. |
