Early after-depolarisations induced by noradrenaline may be initiated by calcium released from sarcoplasmic reticulum
We investigated the effect of 10−8 M noradrenaline (NA) on [Ca2+]i and electrical activity of single myocytes of guinea-pig ventricular myocardium loaded with Indo 1-AM. Membrane potential was recorded by means of the patch electrode and patch amplifier set to the currentclamp mode. Cells were stimulated at a rate of 30/min by 3 ms pulses of the current injected through the recording electrode. Superfusion of NA resulted in slight shortening of action potentials (APs), increase in rate of rise and amplitude of the respective Ca2+ transients, and appearance of secondary Ca2+ transients of two kinds: 1. appearing before repolarisation of AP and decay of the preceding Ca2+ transient were completed and 2. appearing between the APs. We named them early after-transients (EAT) and delayed after-transients (DAT), respectively. Without any additional intervention EATs caused some prolongation of APs duration and DATs resulted in subthreshold delayed after-depolarisations (DADs). When sarcolemmal K+ conductance was decreased by tetraethylammonium (TEA) in the patch electrode or 20 µM BaCl2 in the Tyrode solution, EATs initiated early after depolarizations (EADs) and DATs initiated suprathreshold DADs triggering full-sized APs. Superfusion of 30.0 mM Na+ (replaced with LiCl) resulted in reduction of AP duration by ~70% and appearance of DATs. Also, the frequent multiple oscillations of Ca2+ concentration were often observed. Neither DATs nor the oscillations had any affect on electrical activity of the cells. Their electrogenicity could not be increased by TEA or 20.0 µM Ba2+. EATs and DATs and their respective EADs and DADs could not be initiated by NA or low Na+ superfusion in the cells pretreated with 2 × 10−7 M thapsigargin, a selective blocker of Ca2+-ATPase of sarcoplasmic reticulum (SR). We conclude that in contrast to the current hypothesis, EADs can be initiated by Ca2+ released early in the cardiac cycle from the overloaded SR, and that electrogenicity of both types of Ca2+ oscillations critically depends on the sarcolemmal K+ conductance.
Key wordscardiac myocytes early after depolarisations delayed after depolarisations calcium sarcoplasmic reticulum noradrenaline
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- 1.Cranefield PF: Action potentials, afterpotentials, and arrhythmias. Circ Res 41: 414–423, 1977Google Scholar
- 17.Rousseau E, Smith JS, Meissner G: Ryanodine modifies conductance and gating behavior of single Ca2+ release channels. Am J Physiol 256:C813–C822, 1987Google Scholar
- 19.Bassani JWM, Bassani RA, Bers DM: Relaxation in rabbit and rat cardiac cells: species-dependent differences in cellular mechanisms. J Physiol (Lond) 476: 279–293, 1994Google Scholar
- 20.Janczewski A M, Lakatta E G: Sarcoplasmic reticulum buffers calcium influx during the action potential in guinea-pig ventricular myocytes. J Physiol (Lond). 471: 343–363, 1993Google Scholar
- 27.Fedida D, Noble D, Shimoni Y, Spindler A. J: Inward current related to contraction in guinea-pig ventricular myocytes. J Physiol (Lond) 385:565–589, 1987Google Scholar
- 29.Egan TM, Noble D, Noble SJ, Powell Y, Spindler AJ, Twist VW: Sodium-calcium exchange during the action potential in guinea-pig ventricular cells. J. Physiol. (Lond). 411: 639–661, 1989Google Scholar