Sustained subthreshold-for-twitch depolarization in rat single ventricular myocytes causes sustained calcium channel activation and sarcoplasmic reticulum calcium release.

Abstract

Single rat ventricular myocytes, voltage-clamped at -50 to -40 mV, were depolarized in small steps in order to define the mechanisms that govern the increase in cytosolic [Ca ~+] (Ca i) and contraction, measured as a reduction in myocyte length. Small (3-5 mV), sustained (seconds) depolarizations that caused a small inward or no detectable change in current were followed after a delay by small (<2% of the resting length), steady reductions in cell length measured via a photodiode array, and small, steady increases in Ca i measured by changes in Indo-1 fluorescence. Larger (greater than -30 and less than -20 mV), sustained depolarizations produced phasic Ca 2+ currents, Ca i transients, and twitch contractions, followed by a steady current and a steady increase in Ca~ and contraction. Nitrendipine (or Cd, verapamil, or Ni) abolished the steady contraction and always produced an outward shift in steady current. The steady, nitrendipine-sensitive current and sustained increase in Ca i and contraction exhibited a similar voltage dependence over the voltage range between -40 and -20 mV. 2/zM ryanodine in the presence of intact Ca 2+ channel activity also abolished the steady increase in Cal and contraction over this voltage range. We conclude that when a sustained depolarization does not exceed about -20 mV, the resultant steady, graded contraction is due to SR Ca 2+ release graded by a steady ("window") Ca 2 § current. The existence of appreciable, sustained, graded Ca 2 § release in response to Ca ~+ current generated by arbitrarily small depolarizations is not compatible with any model of Ca2+-induced Ca ~+ release in which the releasing effect of the Ca 2+

Increases in diastolic [Ca2+] can contribute to positive inotropy in guinea pig ventricular myocytes in the absence of changes in amplitudes of Ca2+ transients

“…Previous studies have shown that 100 M Cd 2ϩ blocks I Ca-L window current (35). Interestingly, when we blocked I Ca-L window currents with 100 M Cd 2ϩ , we found that diastolic Ca 2ϩ levels still increased in 5.0 mM extracellular [Ca 2ϩ ].…”

Characteristics of Ca2+ release induced by Ca2+ influx in cultured bullfrog sympathetic neurones.

“…Wier, 1990). Furthermore, a sustained and graded release of Ca2+ in constant amplitude was found to occur through a CICR mechanism by a sustained Ca2' entry at the cell membrane in rat ventricular myocytes (Talo, Stern, Spurgeon, Isenberg & Lakatta, 1990).…”

Ca(2+)‐dependent heat production under basal and near‐basal conditions in the mouse soleus muscle.

“…Similarly, in isolated cardiomyocytes, it was recently shown that the sustained increase of Ca?+ observed under subthreshold-for-twitch depolarization requires functional SR Ca2+ channels (Talo et al 1990). Since the absolute rate of Ca2+ entry across the plasmalemma probably remained very low during subthreshold depolarization, even if it was doubled under 15 mM-extracellular K+ as in smooth muscle (Cattaneo, Gende, Cingolani & Venosa, 1991), these results strongly support the idea that Ca2+ recirculation occurs at much larger rates across the SR membrane than across the sarcolemma during near-basal and basal steady states.…”

“…More recently, it was shown that sustained sarcolemmal depolarizations of only a few millivolts produce sustained, albeit small increases of Ca2+ in frog skeletal muscle (Snowdowne, 1985) and in rat ventricular myocytes (Talo, Stern, Spurgeon, Isenberg & Lakatta, 1990). This, together with the present results showing that high Mg2+, dantrolene or BDM suppressed most of the increase in E and 02 consumption induced by relatively small changes of K+ (Figs 3-5), strongly suggests that the sustained increase in metabolic rate during subthreshold-for-contracture depolarizations is essentially caused by an increased energy cost of Ca?+ homeostasis.…”