Calcium permeability increase of endplate channels in rat muscle during postnatal development

1. Patches of endplate membrane were isolated from rat flexor digitorum brevis muscle at different postnatal stages to measure the time course of developmental changes in conductance, deactivation time constant and relative Ca²⁺ permeability of endplate channels. 2. The predominant channel conductance was 40 ± 1 pS (n = 9) at postnatal day 9 (P9) or younger whereas it was 59 ± 3 pS (n = 5) at P21 or in older muscle. The deactivation time constant of ensemble patch currents evoked by brief ACh application, decreased from 8 ± 3 ms (n = 45) at P5-9 to 2.3 ± 0.3 ms (n = 5) in P21-28 muscle. 3. The relative Ca²⁺ permeability, measured by the shift of biionic (Ca²⁺/Cs⁺) reversal potential of ensemble patch currents upon the replacement of high [Cs⁺] by high [Ca²⁺] extracellular solution and with Cs+ as internal reference ion, increased during postnatal development. The biionic reversal potential shift changed from -21 ± 1 mV (n = 8) at P5 to -8 ± 1 mV (n = 10) in P15 or older muscle. 4. Recombinant γ-AChR channels expressed in Xenopus laevis oocytes had a biionic (Ca²⁺/Cs⁺) reversal potential shift of -24.9 ± 2 mV (n = 14) comparable to that of neonatal endplate channels whereas the reversal potential shift for recombinant ε-AChR channels was -7.6 ± 0.9 mV (n = 13), comparable to that of endplate channels in adult muscle. 5. It is concluded that an approximately 3-fold increase in Ca²⁺ current through endplate channels during postnatal development is caused by replacement of the fetal γ-subunit by the ε-subunit in juvenile and adult muscle.