ATP-induced cytoplasmic [Ca2+]increases in isolated cochlear outer hair cells. Involved receptor and channel mechanisms
| Autor: | E. Heilbronn, R. Nilles, Hans P. Zenner, L. Järlebark |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
Cytoplasm G protein Guinea Pigs Fluorescence spectrometry In Vitro Techniques Biology Ligands Pertussis toxin Adenosine Triphosphate GTP-Binding Proteins Animals Channel blocker Virulence Factors Bordetella Ion transporter Membrane potential Phospholipase C Purinergic receptor Receptors Purinergic Calcium Channel Blockers Sensory Systems Hair Cells Auditory Outer Spectrometry Fluorescence Pertussis Toxin Biochemistry Biophysics Calcium Female Calcium Channels Fura-2 Signal Transduction |
| Zdroj: | Hearing Research. 73:27-34 |
| ISSN: | 0378-5955 |
| DOI: | 10.1016/0378-5955(94)90279-8 |
| Popis: | Outer hair cells (OHC) of the mammalian cochlea are thought to preprocess the sound signal by active movements, which can be induced by electrical or chemical stimulation, e.g. depolarization evoked by high [K + ]or increased cytoplasmic [Ca 24 ]. Extracellular ATP has been found to induce cytoplasmic [Ca 2 + ]increases in OHC but involved mechanisms have not been elucidated. Cytoplasmic [Ca 2+ ]was measured in non-enzymatically isolated single OHC using Fura-2 microspectrometry. Results, using ATP/derivatives and other P 2 -purinergic receptor (P 2 R) ligands, as well as Ca 2+ -channel blockers and pertussis toxin, revealed several signal transduction pathways that increase cytoplasmic [Ca 2 + ]in OHC: a P 2 -purinergic receptor (P 2 R) -G-protein - effector (phospholipase C or an ion channel) system and a voltage-dependent Ca 2+ channel. Agonist potency studies denote a pattern analogous to that found in skeletal muscle, i.e. ATP- α -S > ATP = 2-methyl-S-ATP > ADP > α ,β-methylene- but no activation by ADPβF or UTP, leaving a choice of P 2y or P 2z R subtypes. The latter possibility gained strength from calculations showing that up to 8% of ATP may have formed the P 2z R agonist ATP 4− in the experimental medium. Experiments in Ca 2+ -free medium and with pertussis toxin revealed that the main Ca 2 + source was intracellular. Pertussis toxin did not affect [Ca 2 + ]increase induced by carbachol. Acetylcholine, administered a few seconds before ATP. did not affect total cytoplasmic [Ca 2+ ]increases. Induced cytoplasmic [Ca 2 + ]increases were high enough ( > 500 nM at 50 μM ATP/ derivatives) to hyperpolarize the OHC membrane by opening K + -channels and decreased little with time. Artifacts may have been caused by the sustained Ca 2+ levels, e.g. activation of proteases by the high cytoplasmic [Ca 2+ ]. Similar events in vivo may have pathological consequences. |
| Databáze: | OpenAIRE |
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