Early after-depolarisations induced by noradrenaline may be initiated by calcium released from sarcoplasmic reticulum
✍ Scribed by Robert Janiak; Bohdan Lewartowski
- Publisher
- Springer
- Year
- 1996
- Tongue
- English
- Weight
- 543 KB
- Volume
- 163-164
- Category
- Article
- ISSN
- 0300-8177
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✦ Synopsis
We investigated the effect of 104 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 current clamp 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 Ca 2+ transients, and appearance of secondary Ca 2+ transients of two kinds: 1. appearing before repolarisation of AP and decay of the preceding Ca 2+ 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/aM BaC12 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 LiC1) resulted in reduction of AP duration by-70% and appearance of DATs. Also, the frequent multiple oscillations of Ca 2+ 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 laM Ba 2+. 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 x 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 Ca 2+ released early in the cardiac cycle from the overloaded SR, and that electrogenicity of both types of Ca 2+ oscillations critically depends on the sarcolemmal K + conductance. (Mol Cell Biochem 163/164: 125-130, 1996)