Regulation of Ca2+-activated K+ channels by multifunctional Ca2+/calmodulin-dependent protein kinase

Steven Claude Sansom, Rong Ma, Pamela K Carmines, David A. Hall

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Abstract

Activation of mesangial cells by ANG II provokes release of intracellular Ca2+ stores and subsequent Ca2+ influx through voltage-gated channels, events that are reflected by a large transient increase in intracellular concentration [Ca2+](i) followed by a modest sustained elevation in [Ca2+](i). These ANG II-induced alterations in [Ca2+](i) elicit activation of large Ca2+-activated K+ channels (BK(Ca)) in a negative-feedback manner. The mechanism of this BK(Ca) feedback response may involve the direct effect of intracellular Ca2+ on the channel and/or channel activation by regulatory enzymes. The present study utilized patch-clamp and fura 2 fluorescence techniques to assess the involvement of multifunctional calcium calmodulin kinase II (CAMKII) in the BK(Ca) feedback response. In cell-attached patches, KN62 (specific inhibitor of CAMKII) either abolished or reduced to near zero the ANG II-induced BK(Ca) feedback response. This phenomenon did not reflect direct effects of KN62 on the BK(Ca) channel, because this agent alone did not significantly alter BK(Ca) channel activity in inside-out patches. KN62 also failed to alter either the transient peak or sustained plateau phases of the [Ca2+](i) response to ANG II. In inside-out patches (1 μM Ca2+ in bath), calmodulin plus ATP activated BK(Ca) channels in the presence but not the absence of CAMKII. These observations are consistent with the postulate that CAMKII is involved in the BK(Ca) feedback response of mesangial cells, acting to potentiate the influence of increased [Ca2+](i) on the BK(Ca) channel or a closely associated regulator of the channel. An additional effect of CAMKII to activate a voltage-gated Ca2+ channel cannot be ruled out by these experiments.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume279
Issue number2 48-2
StatePublished - Sep 18 2000

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Calcium-Activated Potassium Channels
Calcium-Calmodulin-Dependent Protein Kinases
Large-Conductance Calcium-Activated Potassium Channels
Mesangial Cells
Enzyme Activation
Fura-2
Calmodulin
Baths
Adenosine Triphosphate
Fluorescence
Calcium

Keywords

  • Angiotensin II
  • Fura 2
  • Mesangial cells
  • Patch clamp

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

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title = "Regulation of Ca2+-activated K+ channels by multifunctional Ca2+/calmodulin-dependent protein kinase",
abstract = "Activation of mesangial cells by ANG II provokes release of intracellular Ca2+ stores and subsequent Ca2+ influx through voltage-gated channels, events that are reflected by a large transient increase in intracellular concentration [Ca2+](i) followed by a modest sustained elevation in [Ca2+](i). These ANG II-induced alterations in [Ca2+](i) elicit activation of large Ca2+-activated K+ channels (BK(Ca)) in a negative-feedback manner. The mechanism of this BK(Ca) feedback response may involve the direct effect of intracellular Ca2+ on the channel and/or channel activation by regulatory enzymes. The present study utilized patch-clamp and fura 2 fluorescence techniques to assess the involvement of multifunctional calcium calmodulin kinase II (CAMKII) in the BK(Ca) feedback response. In cell-attached patches, KN62 (specific inhibitor of CAMKII) either abolished or reduced to near zero the ANG II-induced BK(Ca) feedback response. This phenomenon did not reflect direct effects of KN62 on the BK(Ca) channel, because this agent alone did not significantly alter BK(Ca) channel activity in inside-out patches. KN62 also failed to alter either the transient peak or sustained plateau phases of the [Ca2+](i) response to ANG II. In inside-out patches (1 μM Ca2+ in bath), calmodulin plus ATP activated BK(Ca) channels in the presence but not the absence of CAMKII. These observations are consistent with the postulate that CAMKII is involved in the BK(Ca) feedback response of mesangial cells, acting to potentiate the influence of increased [Ca2+](i) on the BK(Ca) channel or a closely associated regulator of the channel. An additional effect of CAMKII to activate a voltage-gated Ca2+ channel cannot be ruled out by these experiments.",
keywords = "Angiotensin II, Fura 2, Mesangial cells, Patch clamp",
author = "Sansom, {Steven Claude} and Rong Ma and Carmines, {Pamela K} and Hall, {David A.}",
year = "2000",
month = "9",
day = "18",
language = "English (US)",
volume = "279",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
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TY - JOUR

T1 - Regulation of Ca2+-activated K+ channels by multifunctional Ca2+/calmodulin-dependent protein kinase

AU - Sansom, Steven Claude

AU - Ma, Rong

AU - Carmines, Pamela K

AU - Hall, David A.

PY - 2000/9/18

Y1 - 2000/9/18

N2 - Activation of mesangial cells by ANG II provokes release of intracellular Ca2+ stores and subsequent Ca2+ influx through voltage-gated channels, events that are reflected by a large transient increase in intracellular concentration [Ca2+](i) followed by a modest sustained elevation in [Ca2+](i). These ANG II-induced alterations in [Ca2+](i) elicit activation of large Ca2+-activated K+ channels (BK(Ca)) in a negative-feedback manner. The mechanism of this BK(Ca) feedback response may involve the direct effect of intracellular Ca2+ on the channel and/or channel activation by regulatory enzymes. The present study utilized patch-clamp and fura 2 fluorescence techniques to assess the involvement of multifunctional calcium calmodulin kinase II (CAMKII) in the BK(Ca) feedback response. In cell-attached patches, KN62 (specific inhibitor of CAMKII) either abolished or reduced to near zero the ANG II-induced BK(Ca) feedback response. This phenomenon did not reflect direct effects of KN62 on the BK(Ca) channel, because this agent alone did not significantly alter BK(Ca) channel activity in inside-out patches. KN62 also failed to alter either the transient peak or sustained plateau phases of the [Ca2+](i) response to ANG II. In inside-out patches (1 μM Ca2+ in bath), calmodulin plus ATP activated BK(Ca) channels in the presence but not the absence of CAMKII. These observations are consistent with the postulate that CAMKII is involved in the BK(Ca) feedback response of mesangial cells, acting to potentiate the influence of increased [Ca2+](i) on the BK(Ca) channel or a closely associated regulator of the channel. An additional effect of CAMKII to activate a voltage-gated Ca2+ channel cannot be ruled out by these experiments.

AB - Activation of mesangial cells by ANG II provokes release of intracellular Ca2+ stores and subsequent Ca2+ influx through voltage-gated channels, events that are reflected by a large transient increase in intracellular concentration [Ca2+](i) followed by a modest sustained elevation in [Ca2+](i). These ANG II-induced alterations in [Ca2+](i) elicit activation of large Ca2+-activated K+ channels (BK(Ca)) in a negative-feedback manner. The mechanism of this BK(Ca) feedback response may involve the direct effect of intracellular Ca2+ on the channel and/or channel activation by regulatory enzymes. The present study utilized patch-clamp and fura 2 fluorescence techniques to assess the involvement of multifunctional calcium calmodulin kinase II (CAMKII) in the BK(Ca) feedback response. In cell-attached patches, KN62 (specific inhibitor of CAMKII) either abolished or reduced to near zero the ANG II-induced BK(Ca) feedback response. This phenomenon did not reflect direct effects of KN62 on the BK(Ca) channel, because this agent alone did not significantly alter BK(Ca) channel activity in inside-out patches. KN62 also failed to alter either the transient peak or sustained plateau phases of the [Ca2+](i) response to ANG II. In inside-out patches (1 μM Ca2+ in bath), calmodulin plus ATP activated BK(Ca) channels in the presence but not the absence of CAMKII. These observations are consistent with the postulate that CAMKII is involved in the BK(Ca) feedback response of mesangial cells, acting to potentiate the influence of increased [Ca2+](i) on the BK(Ca) channel or a closely associated regulator of the channel. An additional effect of CAMKII to activate a voltage-gated Ca2+ channel cannot be ruled out by these experiments.

KW - Angiotensin II

KW - Fura 2

KW - Mesangial cells

KW - Patch clamp

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M3 - Article

VL - 279

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 2 48-2

ER -