Stimulation of Ca-induced Ca release only transiently increases the systolic Ca transient: measurements of Ca fluxes and sarcoplasmic reticulum Ca.

نویسندگان

  • A W Trafford
  • M E Díaz
  • D A Eisner
چکیده

OBJECTIVE To investigate the effects of stimulating calcium induced Ca release with low concentrations (100-200 microM) of caffeine and, in particular, to study the cellular mechanisms responsible for the transient responses found previously. METHODS Experiments were performed on isolated rat ventricular myocytes. Intracellular calcium concentration ([Ca2+]i) was measured with Indo-1, the cells were voltage-clamped with the perforated patch technique and sarcoplasmic reticulum (s.r.) Ca content was estimated from the integral of the caffeine-evoked current. RESULTS The systolic Ca transient produced by the first depolarization in the presence of caffeine was larger than the control. Over the next few pulses the magnitude of the Ca transient returned to control levels despite the maintained presence of caffeine. The s.r. Ca content was decreased by 9% after one pulse in caffeine and by 21% after several pulses in caffeine. The first pulse in the low concentration of caffeine was followed by an enhanced inward (Na-Ca exchange) current tail indicating increased efflux of calcium from the cell. The extra loss of calcium calculated from the tail current agreed quantitatively with that from the change of s.r. Ca content. CONCLUSIONS These results show that stimulating calcium induced calcium release produces only a transient increase of the systolic Ca transient. This is due to the larger Ca transient decreasing the s.r. Ca content. It is concluded that any agent whose sole mode of action is stimulation of calcium-induced calcium release will not produce a maintained inotropic effect. The consequences of this for the effects of other modulators of calcium induced calcium release are discussed.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Integrative analysis of calcium signalling in cardiac muscle.

This review discusses the control of the amplitude of the cardiac systolic Ca transient. The Ca transient arises largely from release from the sarcoplasmic reticulum (SR). Release is triggered by calcium-induced calcium release (CICR) whereby the entry of a small amount of Ca on the L-type Ca current, "the trigger", results in the release of much more Ca from the SR. There are three potential c...

متن کامل

Reducing Ryanodine Receptor Open Probability as a Means to Abolish Spontaneous Ca Release and Increase Ca Transient Amplitude in Adult Ventricular Myocytes

The aim of this work was to investigate whether it is possible to remove arrhythmogenic Ca release from the sarcoplasmic reticulum that occurs in calcium overload without compromising normal systolic release. Exposure of rat ventricular myocytes to isoproterenol (1 mol/L) resulted in an increased amplitude of the systolic Ca transient and the appearance of waves of diastolic Ca release. Applica...

متن کامل

Sarcoplasmic reticulum Ca release in intact ventricular myocytes.

Sarcoplasmic reticulum (SR) Ca release in intact ventricular myocytes is the major source of Ca which activates cardiac contraction (although Ca influx makes a non-negligible contribution in most species). The fundamental events of SR Ca release are known as Ca sparks. The twitch Ca transient is composed of approximately 10,000 Ca sparks occurring in a given cell, and they are synchronized by t...

متن کامل

Increasing ryanodine receptor open probability alone does not produce arrhythmogenic calcium waves: threshold sarcoplasmic reticulum calcium content is required.

Diastolic waves of Ca(2+) release have been shown to activate delayed afterdepolarizations as well as some cardiac arrhythmias. The aim of this study was to investigate whether increasing ryanodine receptor open probability alone or in the presence of beta-adrenergic stimulation produces diastolic Ca release from the sarcoplasmic reticulum (SR). When voltage-clamped rat ventricular myocytes wer...

متن کامل

Coordinated Control of Cell Ca Loading and Triggered Release From the Sarcoplasmic Reticulum Underlies the Rapid Inotropic Response to Increased L-Type Ca Current

The aim of this study was to investigate how sarcoplasmic reticulum (SR) Ca content and systolic Ca are controlled when Ca entry into the cell is varied. Experiments were performed on voltage-clamped rat and ferret ventricular myocytes loaded with fluo-3 to measure intracellular Ca concentration ([Ca]i). Increasing external Ca 21 concentration ([Ca]o) from 1 to 2 mmol/L increased the amplitude ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cardiovascular research

دوره 37 3  شماره 

صفحات  -

تاریخ انتشار 1998