ATP-INDUCED CYTOPLASMIC [CA2-CELLS - INVOLVED RECEPTOR AND CHANNEL MECHANISMS(]] INCREASES IN ISOLATED COCHLEAR OUTER HAIR)

Citation
R. Nilles et al., ATP-INDUCED CYTOPLASMIC [CA2-CELLS - INVOLVED RECEPTOR AND CHANNEL MECHANISMS(]] INCREASES IN ISOLATED COCHLEAR OUTER HAIR), Hearing research, 73(1), 1994, pp. 27-34
Citations number
50
Categorie Soggetti
Neurosciences,Acoustics
Journal title
ISSN journal
03785955
Volume
73
Issue
1
Year of publication
1994
Pages
27 - 34
Database
ISI
SICI code
0378-5955(1994)73:1<27:AC[-IR>2.0.ZU;2-L
Abstract
Outer hair cells (OHC) of the mammalian cochlea are thought to preproc ess the sound signal by active movements, which can be induced by elec trical or chemical stimulation, e.g. depolarization evoked by high [K] or increased cytoplasmic [Ca2+]. Extracellular ATP has been found to induce cytoplasmic [Ca2+] increases in OHC but involved mechanisms ha ve not been elucidated. Cytoplasmic [Ca2+] was measured in non-enzymat ically isolated single OHC using Fura-2 microspectrometry. Results, us ing ATP/derivatives and other P-2-purinergic receptor (P(2)R) ligands, as well as Ca2+-channel blockers and pertussis toxin, revealed severa l signal transduction; pathways that increase cytoplasmic [Ca2+] in OH C: a P-2-purinergic receptor (P(2)R) G-protein - effector (phospholipa se C or an ion channel) system and a voltage-dependent Ca2+ channel. A gonist potency studies denote a pattern analogous to that found in ske letal muscle, i.e. ATP-alpha-S > ATP = 2-methyl-S-ATP much greater tha n ADP > alpha,beta-methylene-ATP, but no activation by ADP beta F or U TP, leaving a choice of P-2y or P(2z)R subtypes. The latter possibilit y gained strength from calculations showing that up to 8% of ATP may h ave formed the P(2z)R agonist ATP(4-) in the experimental medium. Expe riments in Ca2+-free medium and with pertussis toxin revealed that the main Ca2+ source was intracellular. Pertussis toxin did not affect [C a2+] increase induced by carbachoI. Acetylcholine, administered a few seconds before ATP, did not affect total cytoplasmic [Ca2+] increases. Induced cytoplasmic [Ca2+] increases were high enough (> 500 nM at 50 mu M ATP/derivatives) to hyperpolarize the OHC membrane by opening K-channels and decreased little with time. Artifacts may have been caus ed by the sustained Ca2+ levels, e.g. activation of proteases by the h igh cytoplasmic [Ca2+]. Similar events in vivo may have pathological c onsequences.