Kinetics on Demand Is a Simple Mathematical Solution that Fits Recorded Caffeine-Induced Luminal SR Ca2+ Changes in Smooth Muscle Cells

PLoS One. 2015 Sep 21;10(9):e0138195. doi: 10.1371/journal.pone.0138195. eCollection 2015.

Abstract

The process of Ca2+ release from sarcoplasmic reticulum (SR) comprises 4 phases in smooth muscle cells. Phase 1 is characterized by a large increase of the intracellular Ca2+ concentration ([Ca2+]i) with a minimal reduction of the free luminal SR [Ca2+] ([Ca2+]FSR). Importantly, active SR Ca2+ ATPases (SERCA pumps) are necessary for phase 1 to occur. This situation cannot be explained by the standard kinetics that involves a fixed amount of luminal Ca2+ binding sites. A new mathematical model was developed that assumes an increasing SR Ca2+ buffering capacity in response to an increase of the luminal SR [Ca2+] that is called Kinetics-on-Demand (KonD) model. This approach can explain both phase 1 and the refractory period associated with a recovered [Ca2+]FSR. Additionally, our data suggest that active SERCA pumps are a requisite for KonD to be functional; otherwise luminal SR Ca2+ binding proteins switch to standard kinetics. The importance of KonD Ca2+ binding properties is twofold: a more efficient Ca2+ release process and that [Ca2+]FSR and Ca2+-bound to SR proteins ([Ca2+]BSR) can be regulated separately allowing for Ca2+ release to occur (provided by Ca2+-bound to luminal Ca2+ binding proteins) without an initial reduction of the [Ca2+]FSR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology*
  • Calcium / metabolism*
  • Guinea Pigs
  • Kinetics
  • Male
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Sarcoplasmic Reticulum / drug effects*
  • Sarcoplasmic Reticulum / metabolism

Substances

  • Caffeine
  • Calcium

Grants and funding

This work was supported by the Consejo Nacional de Ciencia y Tecnologia (MX) grant 128735 to AGH and grant 266919 to NCPR (http://www.conacyt.mx/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.