Transient changes in voltage-clamp pulse duration and amplitude modulate calcium entry and subsequent force production, demonstrating calcium recirculation and negative feedback regulation of inward currents in myocardium.
Provides mechanistic insight into myocardial calcium handling in animals; human translation and clinical relevance remain untested.
Inter-relationships between force, membrane voltage and currents were studied in ferret and guinea-pig papillary muscles using the single sucrose gap technique (37 degrees C). The preparations were held at -90 or -40 mV and depolarized (excited) to 0 mV for 180 ms at 1.0 Hz. At regular intervals the shape of a single clamp pulse (called '1') was varied and its effects were investigated during the same test cycle and in two subsequent test cycles ('2' and '3'). Peak force of contraction 1 (F1) increased with the duration of the test clamp up to 90 ms and was constant thereafter. F1 increased with clamp amplitude (V1) between -30 and 10 mV and decreased at greater amplitudes. This relation was similar to the relation between peak second inward current (I1) and V1. The peak force of contractions 2 and 3 rose with the clamp duration and clamp amplitudes of cycle 1. The relation between F3 and F2 was linear (slope 0.40), except at the lowest and highest F2 values where there was a small deviation. There was an inverse relation between I2 and F2. The results support the idea that increased duration or amplitude of the voltage clamp pulse leads to a greater calcium entry which is manifested in the following potentiated contraction. The relation between F3 and F2 implies that about 40% of calcium recirculates between the contractions. The inverse relationship between F2 and I2 indicates that the second inward current is regulated by release from the sarcoplasmic reticulum via negative feedback.
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Arlock et al. (1990) studied this question.
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