The functional role of cardiac T-tubules explored in a model of rat ventricular myocytes.
نویسندگان
چکیده
The morphology of the cardiac transverse-axial tubular system (TATS) has been known for decades, but its function has received little attention. To explore the possible role of this system in the physiological modulation of electrical and contractile activity, we have developed a mathematical model of rat ventricular cardiomyocytes in which the TATS is described as a single compartment. The geometrical characteristics of the TATS, the biophysical characteristics of ion transporters and their distribution between surface and tubular membranes were based on available experimental data. Biophysically realistic values of mean access resistance to the tubular lumen and time constants for ion exchange with the bulk extracellular solution were included. The fraction of membrane in the TATS was set to 56%. The action potentials initiated in current-clamp mode are accompanied by transient K+ accumulation and transient Ca2+ depletion in the TATS lumen. The amplitude of these changes relative to external ion concentrations was studied at steady-state stimulation frequencies of 1-5 Hz. Ca2+ depletion increased from 7 to 13.1% with stimulation frequency, while K+ accumulation decreased from 4.1 to 2.7%. These ionic changes (particularly Ca2+ depletion) implicated significant decrease of intracellular Ca2+ load at frequencies natural for rat heart.
منابع مشابه
Functional subcellular distribution of β1- and β2-adrenergic receptors in rat ventricular cardiac myocytes
β-adrenergic stimulation is a key regulator of cardiac function. The localization of major cardiac adrenergic receptors (β1 and β2) has been investigated using biochemical and biophysical approaches and has led to contradictory results. This study investigates the functional subcellular localization of β1- and β2-adrenergic receptors in rat ventricular myocytes using a physiological approach. V...
متن کاملDirect Evidence for Microdomain-Specific Localization and Remodeling of Functional L-Type Calcium Channels in Rat and Human Atrial Myocytes
BACKGROUND Distinct subpopulations of L-type calcium channels (LTCCs) with different functional properties exist in cardiomyocytes. Disruption of cellular structure may affect LTCC in a microdomain-specific manner and contribute to the pathophysiology of cardiac diseases, especially in cells lacking organized transverse tubules (T-tubules) such as atrial myocytes (AMs). METHODS AND RESULTS Is...
متن کاملNo apparent requirement for neuronal sodium channels in excitation-contraction coupling in rat ventricular myocytes.
The majority of Na channels in the heart are composed of the tetrodotoxin (TTX)-resistant (KD, 2 to 6 micromol/L) "cardiac" NaV1.5 isoform; however, TTX-sensitive (KD, 1 to 25 nmol/L) "neuronal" Na channel isoforms have recently been detected in several cardiac preparations. In the present study, we determined the functional subcellular localization of Na channel isoforms (according to their TT...
متن کامل-Ca Exchange Activity Is Localized in the T-Tubules of Rat Ventricular Myocytes
Detubulation of rat ventricular myocytes has been used to investigate the role of the t-tubules in Ca cycling during excitation-contraction coupling in rat ventricular myocytes. Ca was monitored using fluo-3 and confocal microscopy. In control myocytes, electrical stimulation caused a spatially uniform increase in intracellular [Ca ] across the cell width. After detubulation, [Ca ] rose initial...
متن کاملSarcolemmal distribution of ICa and INCX and Ca2+ autoregulation in mouse ventricular myocytes
The balance of Ca2+ influx and efflux regulates the Ca2+ load of cardiac myocytes, a process known as autoregulation. Previous work has shown that Ca2+ influx, via L-type Ca2+ current (ICa), and efflux, via the Na+/Ca2+ exchanger (NCX), occur predominantly at t-tubules; however, the role of t-tubules in autoregulation is unknown. Therefore, we investigated the sarcolemmal distribution of ICa an...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Philosophical transactions. Series A, Mathematical, physical, and engineering sciences
دوره 364 1842 شماره
صفحات -
تاریخ انتشار 2006