{'fraction_non_alphanumeric': 0.03653217011995638, 'fraction_numerical': 0.016902944383860415, 'mean_word_length': 5.43859649122807, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Partial inhibition of Ca2+ current by methoxyverapamil (D600) reveals spatial nonuniformities in [Ca2+]i during excitation-contraction coupling in cardiac myocytes.

The laser scanning confocal microscope was used in conjunction with the Ca2+ indicator fluo 3 to examine the spatiotemporal properties of free Ca2+ ([Ca2+]i) transients in isolated rat cardiac myocytes. We show that localized increases in [Ca2+]i (Ca2+ sparks) can be triggered by membrane depolarization in cardiac myocytes when the sarcolemmal Ca2+ current amplitude is reduced by methoxyverapamil (D600). These depolarization-evoked Ca2+ sparks are similar in amplitude and spatiotemporal properties to spontaneous Ca2+ sparks previously observed at rest. These observations support the idea that Ca2+ sparks are the result of the activation of functional elementary units of sarcoplasmic reticulum (SR) Ca2+ release. The synchronous activation of a large number of Ca2+ sparks can explain the increased amplitude and slower time course of the electrically evoked [Ca2+]i transient as well as the presence of spatial nonuniformities in [Ca2+]i during its rise. The data shown here suggest a model for excitation-contraction coupling in which the amplitude of the [Ca2+]i transient is regulated by variations in the probability of recruitment of elementary SR Ca2+ release units as well as the amount of Ca2+ released by each unit. Since the activation of each release unit will depend on the local amplitude of the Ca2+ current, this model can explain the regulation of the amplitude of the [Ca2+]i transient by the Ca2+ current. In addition, these data indicate that caution should be applied to the interpretation of signals obtained with nonlinear Ca2+ indicators during the rising phase of the [Ca2+]i transient, when the nonuniformities in [Ca2+]i are largest.