Cytosolic calcium staircase in ventricular myocytes isolated from guinea pigs and rats.

STUDY OBJECTIVE

The aim was to study intracellular calcium dynamics underlying positive or negative tension staircase of mammalian hearts.

DESIGN

Changes in cytosolic calcium concentration [( Ca2+]i) in single ventricular myocytes were investigated using a Ca2+ indicator, fura-2. Beat to beat alterations in fura-2 fluorescence and cell edge movement on resumption of stimulation were recorded on video tape, and analysed by a computer based image processing system.

EXPERIMENTAL MATERIAL

Single ventricular myocytes were enzymatically isolated from the hearts of 30 adult guinea pigs and 25 adult rats.

MEASUREMENTS AND MAIN RESULTS

In guinea pig ventricular myocytes, the positive contractile staircase was associated with ascending staircases of both peak systolic and end diastolic [Ca2+]i because of a cumulative increase in diastolic [Ca2+]i. In rat ventricular myocytes, the negative contractile staircase was accompanied by a descending staircase of peak systolic [Ca2+]i, while end diastolic [Ca2+]i level was unchanged due to the rapid decay of [Ca2+]i transients. Ryanodine (10 microM) reversed the mode of [Ca2+]i and contractile staircases from negative to positive in rat myocytes, whereas it caused minimal alteration in guinea pig myocytes.

CONCLUSIONS

Tension staircase of mammalian hearts depends on diastolic Ca2+ level as well as Ca2+ handling by the sarcoplasmic reticulum. The positive staircase may require progressive increase in diastolic [Ca2+]i, while the negative staircase may be mediated by depletion of activator Ca2+ in the sarcoplasmic reticulum.