Intracellular Ca transients in rat cardiac myocytes: Role of Na-Ca exchange in excitation-contraction coupling

Donald M Bers, W. J. Lederer, J. R. Berlin

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Membrane current and intracellular Ca concentration ([Ca](i)) transients were recorded from isolated rat ventricular myocytes under voltage-clamp control. The cells were dialyzed by the patch pipette solution, which contained the fluorescent Ca indicator indo-1 and 0.5 mM Na. Under these experimental conditions, Ca entry via Na-Ca exchange did not appear to be appreciable even in the absence of extracellular Na. Increasing the duration of voltage-clamp pulses from 5 to 80 ms produced [Ca](i) transients of increasing amplitude, while the peak Ca current was not changed. This duration dependence of the [Ca](i) transient was most demonstrable at more negative test potentials (e.g., -20 to -30 mV) and was not qualitatively modified by Na-free solutions. This latter result indicates that Ca extrusion by Na-Ca exchange is not responsible for the smaller [Ca](i) transients observed when the membrane is repolarized after very brief depolarizations. Although the peak Ca current was not changed by increasing pulse duration, the integrated Ca current was increased. These observations are consistent with a Ca-release mechanism in cardiac excitation-contraction coupling in which 1) the Ca-release process can be modulated by membrane potential or 2) the Ca entering the cell via Ca channels has a preferential access [compared with Ca from the sarcoplasmic reticulum (SR)] to the site(s) that control SR Ca release. The role of Na-Ca exchange in the decline of [Ca](i) during relaxation was also explored. Removal of extracellular Na (Na(o)) resulted in 20% slowing of the decline in [Ca](i) during relaxation. From this, we conclude that the Na-Ca exchange competes with SR to remove Ca from the cytoplasm and that under our control conditions the exchanger may account for 20 of this decline. The Na(o) dependence of relaxation was reduced at more positive membrane potentials and increased by SR Ca loading.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume258
Issue number5 27-5
StatePublished - 1990
Externally publishedYes

Fingerprint

Excitation Contraction Coupling
Sarcoplasmic Reticulum
Cardiac Myocytes
Rats
Membranes
Clamping devices
Membrane Potentials
Intracellular Membranes
Depolarization
Electric potential
Muscle Cells
Extrusion
Cytoplasm

Keywords

  • calcium current
  • cardiac muscle
  • indo-1

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Intracellular Ca transients in rat cardiac myocytes : Role of Na-Ca exchange in excitation-contraction coupling. / Bers, Donald M; Lederer, W. J.; Berlin, J. R.

In: American Journal of Physiology - Cell Physiology, Vol. 258, No. 5 27-5, 1990.

Research output: Contribution to journalArticle

@article{4be321f0fee44cc0ae78a20ba888bfab,
title = "Intracellular Ca transients in rat cardiac myocytes: Role of Na-Ca exchange in excitation-contraction coupling",
abstract = "Membrane current and intracellular Ca concentration ([Ca](i)) transients were recorded from isolated rat ventricular myocytes under voltage-clamp control. The cells were dialyzed by the patch pipette solution, which contained the fluorescent Ca indicator indo-1 and 0.5 mM Na. Under these experimental conditions, Ca entry via Na-Ca exchange did not appear to be appreciable even in the absence of extracellular Na. Increasing the duration of voltage-clamp pulses from 5 to 80 ms produced [Ca](i) transients of increasing amplitude, while the peak Ca current was not changed. This duration dependence of the [Ca](i) transient was most demonstrable at more negative test potentials (e.g., -20 to -30 mV) and was not qualitatively modified by Na-free solutions. This latter result indicates that Ca extrusion by Na-Ca exchange is not responsible for the smaller [Ca](i) transients observed when the membrane is repolarized after very brief depolarizations. Although the peak Ca current was not changed by increasing pulse duration, the integrated Ca current was increased. These observations are consistent with a Ca-release mechanism in cardiac excitation-contraction coupling in which 1) the Ca-release process can be modulated by membrane potential or 2) the Ca entering the cell via Ca channels has a preferential access [compared with Ca from the sarcoplasmic reticulum (SR)] to the site(s) that control SR Ca release. The role of Na-Ca exchange in the decline of [Ca](i) during relaxation was also explored. Removal of extracellular Na (Na(o)) resulted in 20{\%} slowing of the decline in [Ca](i) during relaxation. From this, we conclude that the Na-Ca exchange competes with SR to remove Ca from the cytoplasm and that under our control conditions the exchanger may account for 20 of this decline. The Na(o) dependence of relaxation was reduced at more positive membrane potentials and increased by SR Ca loading.",
keywords = "calcium current, cardiac muscle, indo-1",
author = "Bers, {Donald M} and Lederer, {W. J.} and Berlin, {J. R.}",
year = "1990",
language = "English (US)",
volume = "258",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "5 27-5",

}

TY - JOUR

T1 - Intracellular Ca transients in rat cardiac myocytes

T2 - Role of Na-Ca exchange in excitation-contraction coupling

AU - Bers, Donald M

AU - Lederer, W. J.

AU - Berlin, J. R.

PY - 1990

Y1 - 1990

N2 - Membrane current and intracellular Ca concentration ([Ca](i)) transients were recorded from isolated rat ventricular myocytes under voltage-clamp control. The cells were dialyzed by the patch pipette solution, which contained the fluorescent Ca indicator indo-1 and 0.5 mM Na. Under these experimental conditions, Ca entry via Na-Ca exchange did not appear to be appreciable even in the absence of extracellular Na. Increasing the duration of voltage-clamp pulses from 5 to 80 ms produced [Ca](i) transients of increasing amplitude, while the peak Ca current was not changed. This duration dependence of the [Ca](i) transient was most demonstrable at more negative test potentials (e.g., -20 to -30 mV) and was not qualitatively modified by Na-free solutions. This latter result indicates that Ca extrusion by Na-Ca exchange is not responsible for the smaller [Ca](i) transients observed when the membrane is repolarized after very brief depolarizations. Although the peak Ca current was not changed by increasing pulse duration, the integrated Ca current was increased. These observations are consistent with a Ca-release mechanism in cardiac excitation-contraction coupling in which 1) the Ca-release process can be modulated by membrane potential or 2) the Ca entering the cell via Ca channels has a preferential access [compared with Ca from the sarcoplasmic reticulum (SR)] to the site(s) that control SR Ca release. The role of Na-Ca exchange in the decline of [Ca](i) during relaxation was also explored. Removal of extracellular Na (Na(o)) resulted in 20% slowing of the decline in [Ca](i) during relaxation. From this, we conclude that the Na-Ca exchange competes with SR to remove Ca from the cytoplasm and that under our control conditions the exchanger may account for 20 of this decline. The Na(o) dependence of relaxation was reduced at more positive membrane potentials and increased by SR Ca loading.

AB - Membrane current and intracellular Ca concentration ([Ca](i)) transients were recorded from isolated rat ventricular myocytes under voltage-clamp control. The cells were dialyzed by the patch pipette solution, which contained the fluorescent Ca indicator indo-1 and 0.5 mM Na. Under these experimental conditions, Ca entry via Na-Ca exchange did not appear to be appreciable even in the absence of extracellular Na. Increasing the duration of voltage-clamp pulses from 5 to 80 ms produced [Ca](i) transients of increasing amplitude, while the peak Ca current was not changed. This duration dependence of the [Ca](i) transient was most demonstrable at more negative test potentials (e.g., -20 to -30 mV) and was not qualitatively modified by Na-free solutions. This latter result indicates that Ca extrusion by Na-Ca exchange is not responsible for the smaller [Ca](i) transients observed when the membrane is repolarized after very brief depolarizations. Although the peak Ca current was not changed by increasing pulse duration, the integrated Ca current was increased. These observations are consistent with a Ca-release mechanism in cardiac excitation-contraction coupling in which 1) the Ca-release process can be modulated by membrane potential or 2) the Ca entering the cell via Ca channels has a preferential access [compared with Ca from the sarcoplasmic reticulum (SR)] to the site(s) that control SR Ca release. The role of Na-Ca exchange in the decline of [Ca](i) during relaxation was also explored. Removal of extracellular Na (Na(o)) resulted in 20% slowing of the decline in [Ca](i) during relaxation. From this, we conclude that the Na-Ca exchange competes with SR to remove Ca from the cytoplasm and that under our control conditions the exchanger may account for 20 of this decline. The Na(o) dependence of relaxation was reduced at more positive membrane potentials and increased by SR Ca loading.

KW - calcium current

KW - cardiac muscle

KW - indo-1

UR - http://www.scopus.com/inward/record.url?scp=0025339902&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025339902&partnerID=8YFLogxK

M3 - Article

C2 - 2333986

AN - SCOPUS:0025339902

VL - 258

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 5 27-5

ER -