RT Journal Article SR Electronic T1 α1E Subunits Form the Pore of Three Cerebellar R-Type Calcium Channels with Different Pharmacological and Permeation Properties JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 171 OP 178 DO 10.1523/JNEUROSCI.20-01-00171.2000 VO 20 IS 1 A1 Tottene, Angelita A1 Volsen, Stephen A1 Pietrobon, Daniela YR 2000 UL http://www.jneurosci.org/content/20/1/171.abstract AB R-type Ca2+ channels cooperate with P/Q- and N-type channels to control neurotransmitter release at central synapses. The leading candidate as pore-forming subunit of R-type channels is the α1E subunit. However, R-type Ca2+ currents with permeation and/or pharmacological properties different from those of recombinant Ca2+channels containing α1E subunits have been described, and therefore the molecular nature of R-type Ca2+channels remains not completely settled. Here, we show that the R-type Ca2+ current of rat cerebellar granule cells consists of two components inhibited with different affinity by the α1E selective antagonist SNX482 (IC50 values of 6 and 81 nm) and a third component resistant to SNX482. The SNX482-sensitive R-type current shows the unique permeation properties of recombinant α1E channels; it is larger with Ca2+ than with Ba2+ as charge carrier, and it is highly sensitive to Ni2+ block and has a voltage-dependence of activation consistent with that of G2 channels with unitary conductance of 15 pS. On the other hand, the SNX482-resistant R-type current shows permeation properties similar to those of recombinant α1A and α1B channels; it is larger with Ba2+ than with Ca2+ as charge carrier, and it has a low sensitivity to Ni2+ block and a voltage-dependence of activation consistent with that of G3 channels with unitary conductance of 20 pS. Gene-specific knock-down by antisense oligonucleotides demonstrates that the different cerebellar R-type channels are all encoded by the α1E gene, suggesting the existence of α1E isoforms with different pore properties.