Ca2+ sparks act as potent regulators of excitation-contraction coupling in airway smooth muscle

J Biol Chem. 2010 Jan 15;285(3):2203-10. doi: 10.1074/jbc.M109.067546. Epub 2009 Nov 17.

Abstract

Ca2+ sparks are short lived and localized Ca2+ transients resulting from the opening of ryanodine receptors in sarcoplasmic reticulum. These events relax certain types of smooth muscle by activating big conductance Ca2+-activated K+ channels to produce spontaneous transient outward currents (STOCs) and the resultant closure of voltage-dependent Ca2+ channels. But in many smooth muscles from a variety of organs, Ca2+ sparks can additionally activate Ca2+-activated Cl(-) channels to generate spontaneous transient inward current (STICs). To date, the physiological roles of Ca2+ sparks in this latter group of smooth muscle remain elusive. Here, we show that in airway smooth muscle, Ca2+ sparks under physiological conditions, activating STOCs and STICs, induce biphasic membrane potential transients (BiMPTs), leading to membrane potential oscillations. Paradoxically, BiMPTs stabilize the membrane potential by clamping it within a negative range and prevent the generation of action potentials. Moreover, blocking either Ca2+ sparks or hyperpolarization components of BiMPTs activates voltage-dependent Ca2+ channels, resulting in an increase in global [Ca2+](i) and cell contraction. Therefore, Ca2+ sparks in smooth muscle presenting both STICs and STOCs act as a stabilizer of membrane potential, and altering the balance can profoundly alter the status of excitability and contractility. These results reveal a novel mechanism underlying the control of excitability and contractility in smooth muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Electric Conductivity
  • Evoked Potentials / drug effects
  • Excitation Contraction Coupling* / drug effects
  • Indicators and Reagents / pharmacology
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Lung*
  • Male
  • Mice
  • Muscle Contraction / drug effects
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiology*

Substances

  • Calcium Channels
  • Indicators and Reagents
  • Large-Conductance Calcium-Activated Potassium Channels
  • Calcium