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• W2065008766 abstract "In cochlea inner hair cells (IHCs), L-type Ca²⁺ channels (LTCCs) formed by α1D subunits (D-LTCCs) possess biophysical and pharmacological properties distinct from those of α1C containing C-LTCCs. We investigated to which extent these differences are determined by α1D itself by analyzing the biophysical and pharmacological properties of cloned human α1D splice variants in tsA-201 cells. Variant α1D_8A,containing exon 8A sequence in repeat I, yielded α1D protein and L-type currents, whereas no intact protein and currents were observed after expression with exon 8B. In whole cell patch-clamp recordings (charge carrier 15–20 mm Ba²⁺), α1D_8A - mediated currents activated at more negative voltages (activation threshold, −45.7 <i>versus</i> −31.5 mV,<i>p</i> < 0.05) and more rapidly (τ_act for maximal inward currents 0.8 <i>versus</i> 2.3 ms;<i>p</i> < 0.05) than currents mediated by rabbit α1C. Inactivation during depolarizing pulses was slower than for α1C (current inactivation after 5-s depolarizations by 90<i>versus</i> 99%, <i>p</i> < 0.05) but faster than for LTCCs in IHCs. The sensitivity for the dihydropyridine (DHP) L-type channel blocker isradipine was 8.5-fold lower than for α1C. Radioligand binding experiments revealed that this was not due to a lower affinity for the DHP binding pocket, suggesting that differences in the voltage-dependence of DHP block account for decreased sensitivity of D-LTCCs. Our experiments show that α1D_8Asubunits can form slowly inactivating LTCCs activating at more negative voltages than α1C. These properties should allow D-LTCCs to control physiological processes, such as diastolic depolarization in sinoatrial node cells, neurotransmitter release in IHCs and neuronal excitability." @default.
• W2065008766 created "2016-06-24" @default.
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• W2065008766 date "2001-06-01" @default.
• W2065008766 modified "2023-10-14" @default.
• W2065008766 title "α1D (Cav1.3) Subunits Can Form L-type Ca2+ Channels Activating at Negative Voltages" @default.
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• W2065008766 doi "https://doi.org/10.1074/jbc.m101469200" @default.
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