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J Physiol Volume 553, Number 3, 747-758, December 15, 2003 DOI: 10.1113/jphysiol.2003.053256
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J Physiol (2003), 553.3, pp. 747-758
© Copyright 2003 The Physiological Society
DOI: 10.1113/jphysiol.2003.053256

Cav1.3 (alpha1D) Ca2+ currents in neonatal outer hair cells of mice

Marcus Michna, Martina Knirsch, Jean-Charles Hoda*, Stefan Muenkner, Patricia Langer, Josef Platzer*, Jörg Striessnig* and Jutta Engel

Institute of Physiology II and Department of Otolaryngology, Tuebingen Hearing Research Centre (THRC), University of Tuebingen, Gmelinstrasse 5, D-72076 Tuebingen, Germany and *Institute of Pharmacy, Department of Pharmacology and Toxicology, Peter-Mayrstrasse 1/I, A-6020 Innsbruck, Austria

Outer hair cells (OHC) serve as electromechanical amplifiers that guarantee the unique sensitivity and frequency selectivity of the mammalian cochlea. It is unknown whether the afferent fibres connected to adult OHCs are functional. If so, voltage-activated Ca2+ channels would be required for afferent synaptic transmission. In neonatal OHCs, Ca2+ channels seem to play a role in maturation since OHCs from Cav1.3-deficient (Cav1.3-/-) mice degenerate shortly after the onset of hearing. We therefore studied whole-cell Ca2+ currents in outer hair cells aged between postnatal day 1 (P1) and P8. OHCs showed a rapidly activating inward current that was 1.8 times larger with 10 mM Ba2+ as charge carrier (IBa) than with equimolar Ca2+ (ICa). IBa started activating at -50 mV with Vmax = -1.9 ± 6.9 mV, V0.5 = -15.0 ± 7.1 mV and k = 8.2 ± 1.1 mV (n = 34). The peak IBa showed negligible inactivation (3.6 % after 300 ms) whereas the ICa (10 mM Ca2+) was inactivated by 50.7 %. OHC IBa was reduced by 33.5 ± 10.3 % (n = 14) with 10 µM nifedipine and increased to 178.5 ± 57.8 % (n = 14) by 5 µM Bay K 8644. A dose-response curve for nifedipine revealed an IC50 of 2.3 µM, a Hill coefficient of 2.7 and a maximum block of 36 %. Average IBa density in OHCs was 24.4 ± 10.8 pA pF-1 (n = 105) which is only 38 % of the value in inner hair cells. Single cell RT-PCR revealed expression of Cav1.3 in OHCs. In OHCs from Cav1.3-/- mice, Ba2+ current density was reduced to 0.6 ± 0.5 pA pF-1 (n = 9) indicating that > 97 % of the Ca2+ channel current in OHCs flows through Cav1.3.



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