a 2007

Modelling t-tubule function in cardiac ventricular myocytes

PÁSEK, Michal; Jiří ŠIMURDA; Georges CHRISTÉ a Clive ORCHARD

Základní údaje

Originální název

Modelling t-tubule function in cardiac ventricular myocytes

Název česky

Modelování funkce t-tubulů u srdečních komorových buněk

Autoři

PÁSEK, Michal; Jiří ŠIMURDA; Georges CHRISTÉ a Clive ORCHARD

Vydání

Life Sciences 2007 (Glasgow), 2007

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

10610 Biophysics

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/07:00033625

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

cardiac cell; tubular system; quantitative modelling

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 3. 1. 2010 18:03, doc. Ing. Michal Pásek, Ph.D.

Anotace

V originále

Cardiac transverse (t-) tubules form a complex network of membrane invaginations in mammalian ventricular myocytes, also known as the transverse-axial tubular system (TATS). Biophysically realistic computer models have been used to investigate experimental ambiguities and aspects of TATS function not currently amenable to experimental investigation: 1. Fraction of cell membrane within the TATS: Detubulation of rat ventricular myocytes causes a ~32% decrease of membrane capacitance whereas optical measurements suggest ~56% of the cell membrane within the TATS. Analysis of factors that may account for this discrepancy, and calculation of the combinations of t-tubule radius, length and density that produce t-tubular membrane fractions of 32% or 56%, suggest that the true fraction is at the upper end of this range. 2. Electrical coupling between the surface and TATS membranes: It has long been speculated that voltage control within the TATS may be inadequate, allowing voltage escape. Analysis based on cable theory, and simulations using models in voltage and current clamp mode, show that voltage spread across both membranes and its equilibration due to their tight electrical coupling is very fast (within 20 microseconds); thus membrane voltage is almost homogeneous over the whole cell membrane during activity. 3. Ion diffusion within TATS: The complexity of the TATS appears to restrict ion diffusion in the TATS lumen. Simulations performed using a model of a single tubule suggest that variable diameter along the length of the tubule and ion buffers in the tubule lumen play a major role in the restricted diffusion and thus in the slowed ion exchange between the TATS lumen and extracellular space. 4. Ion concentration changes in TATS and their consequences: Recent detubulation experiments suggest that many trans-membrane ion flux pathways (for ICa, INaCa, INaK and others) are located predominantly within the TATS. Incorporation of this distribution, and restricted diffusion between the tubular and extracellular spaces, into rat and guinea pig models results in changes of tubular [Ca2+] and [K+] during activity, which depend on stimulation rate. These changes (particularly Ca2+ depletion) cause a significant decrease of intracellular Ca2+ load and hence Ca2+ transient amplitude. These data suggest that the TATS may play an important role in modulating cardiac cell function.

Česky

Abstrakt shrnuje nejnovější poznatky o funkci transverzálně-axiálního tubulárního systému získané prostřednictvím výpočtového modelování.

Návaznosti

MSM0021622402, záměr
Název: Časná diagnostika a léčba kardiovaskulárních chorob
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Časná diagnostika a léčba kardiovaskulárních chorob