Elsevier

Hearing Research

Volume 114, Issues 1–2, December 1997, Pages 107-116
Hearing Research

Research paper
cAMP increases K+ secretion via activation of apical IsK/KvLQT1 channels in strial marginal cells

https://doi.org/10.1016/S0378-5955(97)00152-4Get rights and content

Abstract

In the cochlea, K+ is secreted by electrodiffusion across the apical membrane of strial marginal cells via the IsK/KvLQTI (‘IsK’) channel. This channel complex has been reported to be activated in other systems by adenosine 3′,5′-cyclic monophosphate (cAMP). Since several reports had suggested that cAMP is a second messenger in the cochlea, the effect of the cAMP pathway on transepithelial K+ secretion by strial marginal cells of the gerbil was studied. Both the transepithelial current (Isc) and K+ flux (JK) across strial marginal cell epithelium were measured; Isc in a micro-Ussing chamber and JK as the gradient of K+ concentration near the apical membrane. The apical membrane current (IIsK) and conductance gIsK) of IsK channels were recorded with the on-cell macro-patch and the nystatin-perforated whole-cell patch clamp techniques. It has previously been shown that the apical IsK channel constitutes the primary pathway for K+ secretion. Cytoplasmic cAMP was elevated by applying dibutyryl cyclic-AMP (dbcAMP) or the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX) at 37°C. dbcAMP (1 mM) increased Isc by 51 ± 4% and IIsK in on-cell and whole-cell recordings increased by 214 ± 63% and 390 ± 61% above the control value, respectively. IBMX (1 mM) caused transient increases of Isc by 53 ± 3% and IIsK in on-cell recordings by 177 ± 75% above the control value. The leak conductance due to all non-IsK channel sources did not change in the presence of dbcAMP or IBMX. dbcAMP (1 mM at 24°C) increased JK by 53 ± 16% and Isc by 18 ± 4%. IBMX (1 mM at 24°C) had no effect, suggesting reduced activity of adenylate cyclase at this temperature. Our results demonstrate that the cAMP pathway is constitutively active in strial marginal cells and that the cAMP pathway stimulates transepithelial K+ secretion by increasing ISK channel current rather than by altering another transport pathway.

References (50)

  • J. Schacht

    Hormonal regulation of adenylate cyclase in the stria vascularis of the mouse

    Hear. Res.

    (1985)
  • H. Sunose et al.

    Voltage-activated K channel in luminal membrane of marginal cells of stria vascularis dissected from guinea pig

    Hear. Res.

    (1994)
  • S. Takeuchi et al.

    Ca2+-activated nonselective cation, maxi K+ and Cl channels in apical membrane of marginal cells of stria vascularis

    Hear. Res.

    (1992)
  • D.E. Vetter et al.

    Inner ear defects induced by null mutation of the isk gene

    Neuron

    (1996)
  • P. Wangemann

    Comparison of ion transport mechanisms between vestibular dark cells and strial marginal cells

    Hear. Res.

    (1995)
  • P. Wangemann et al.

    The membrane potential of vestibular dark cells is controlled by a large Cl- conductance

    Hear. Res.

    (1992)
  • P. Wangemann et al.

    Ion transport mechanisms responsible for K' secretion and the transepithelial voltage across marginal cells of stria vascularis in vitro

    Hear. Res.

    (1995)
  • P. Wangemann et al.

    K+-induced stimulation of K+ secretion involves activation of the IsK channel in vestibular dark cells

    Hear. Res.

    (1996.)
  • T. Yamagishi et al.

    Relaxant mechanisms of cyclic AMP-increasing agents in porcine coronary artery

    Eur. J. Pharmacol.

    (1994)
  • G. Zajic et al.

    Cellular localization of adenylate cyclase in the developing and mature inner ear of the mouse

    Hear. Res.

    (1983)
  • P. Ahlström et al.

    Cyclic AMP and adenylate cyclase in the inner ear

    Laryngoscope

    (1975)
  • Q. Al Awgati

    Regulation of membrane transport by endocytotic removal and exocytotic insertion of transporters

    Methods Enzymol.

    (1989)
  • R. Bakker et al.

    Further evidence for the regulation of the tight junction ion selectivity by cAMP in goldfish intestinal mucosa

    J. Membr. Biol.

    (1989)
  • J. Barhanin et al.

    KvLQTI and IsK (minK) proteins associate to form the IKs cardiac potassium current

    Nature

    (1996)
  • E.M. Blumenthal et al.

    Modulation by CAMP of a slowly activating potassium channel expressed in Xenopus oocytes

    J. Neurosci.

    (1992)
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