Adenine nucleoside diphosphates block adaptation of mechanoelectrical transduction in hair cells

Peter Barr-Gillespie, A. J. Hudspeth

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

By adapting to sustained stimuli, hair cells in the internal ear retain their sensitivity to minute transient displacements. Because one model for adaptation asserts that this process is mediated by a myosin isozyme, we reasoned that we should be able to arrest adaptation by interfering with myosin's ATPase cycle though introduction of ADP into hair cells. During tight-seal, whole-cell recordings of transduction currents in cells isolated from bullfrog (Rana catesbeiana) sacculus, dialysis with 5-25 mM ADP gave variable results. In half of the cells examined, the rate of adaptation remained unchanged or even increased; adaptation was blocked in the remaining cells. Because we suspected that the variable effect of ADP resulted from the conversion of ADP to ATP by adenylate kinase, we employed the ADP analog adenosine 5′-[β-thio]diphosphate (ADP[βS]), which is not a substrate for adenylate kinase. Adaptation consistently disappeared in the presence of 1-10 mM ADP[βS]; in addition, the transduction channels' open probability at rest grew from ≈0.1 to 0.8 or more. Both effects could be reversed by 2 mM ATP. When used in conjunction with the adenylate kinase inhibitor P1,P5-bis(5′-adenosyl) pentaphosphate (Ap5A), ADP had effects similar to those of ADP[βS]. These results suggest that adaptation by hair cells involves adenine nucleotides, and they lend support to the hypothesis that the adaptation process is powered by a myosin motor.

Original languageEnglish (US)
Pages (from-to)2710-2714
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number7
StatePublished - Apr 1 1993
Externally publishedYes

Fingerprint

Diphosphates
Adenine
Nucleosides
Adenosine Diphosphate
Adenylate Kinase
Myosins
Rana catesbeiana
Adenosine Triphosphate
Adenine Nucleotides
Patch-Clamp Techniques
Inner Ear
Adenosine
Isoenzymes
Dialysis
adenosine 5'-O-(2-thiodiphosphate)

Keywords

  • Auditory system
  • Ear
  • Molecular motor
  • Myosin
  • Vestibular system

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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abstract = "By adapting to sustained stimuli, hair cells in the internal ear retain their sensitivity to minute transient displacements. Because one model for adaptation asserts that this process is mediated by a myosin isozyme, we reasoned that we should be able to arrest adaptation by interfering with myosin's ATPase cycle though introduction of ADP into hair cells. During tight-seal, whole-cell recordings of transduction currents in cells isolated from bullfrog (Rana catesbeiana) sacculus, dialysis with 5-25 mM ADP gave variable results. In half of the cells examined, the rate of adaptation remained unchanged or even increased; adaptation was blocked in the remaining cells. Because we suspected that the variable effect of ADP resulted from the conversion of ADP to ATP by adenylate kinase, we employed the ADP analog adenosine 5′-[β-thio]diphosphate (ADP[βS]), which is not a substrate for adenylate kinase. Adaptation consistently disappeared in the presence of 1-10 mM ADP[βS]; in addition, the transduction channels' open probability at rest grew from ≈0.1 to 0.8 or more. Both effects could be reversed by 2 mM ATP. When used in conjunction with the adenylate kinase inhibitor P1,P5-bis(5′-adenosyl) pentaphosphate (Ap5A), ADP had effects similar to those of ADP[βS]. These results suggest that adaptation by hair cells involves adenine nucleotides, and they lend support to the hypothesis that the adaptation process is powered by a myosin motor.",
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AU - Hudspeth, A. J.

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N2 - By adapting to sustained stimuli, hair cells in the internal ear retain their sensitivity to minute transient displacements. Because one model for adaptation asserts that this process is mediated by a myosin isozyme, we reasoned that we should be able to arrest adaptation by interfering with myosin's ATPase cycle though introduction of ADP into hair cells. During tight-seal, whole-cell recordings of transduction currents in cells isolated from bullfrog (Rana catesbeiana) sacculus, dialysis with 5-25 mM ADP gave variable results. In half of the cells examined, the rate of adaptation remained unchanged or even increased; adaptation was blocked in the remaining cells. Because we suspected that the variable effect of ADP resulted from the conversion of ADP to ATP by adenylate kinase, we employed the ADP analog adenosine 5′-[β-thio]diphosphate (ADP[βS]), which is not a substrate for adenylate kinase. Adaptation consistently disappeared in the presence of 1-10 mM ADP[βS]; in addition, the transduction channels' open probability at rest grew from ≈0.1 to 0.8 or more. Both effects could be reversed by 2 mM ATP. When used in conjunction with the adenylate kinase inhibitor P1,P5-bis(5′-adenosyl) pentaphosphate (Ap5A), ADP had effects similar to those of ADP[βS]. These results suggest that adaptation by hair cells involves adenine nucleotides, and they lend support to the hypothesis that the adaptation process is powered by a myosin motor.

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