ATP signalling is crucial for the response of human keratinocytes to mechanical stimulation by hypo-osmotic shock

Exp Dermatol. 2011 May;20(5):401-7. doi: 10.1111/j.1600-0625.2010.01219.x. Epub 2011 Feb 28.


Touch is detected through receptors located in the skin and the activation of channels in sensory nerve fibres. Epidermal keratinocytes themselves, however, may sense mechanical stimulus and contribute to skin sensation. Here, we showed that the mechanical stimulation of human keratinocytes by hypo-osmotic shock releases adenosine triphosphate (ATP) and increases intracellular calcium. We demonstrated that the release of ATP was found to be calcium independent because emptying the intracellular calcium stores did not cause ATP release; ATP release was still observed in the absence of external calcium and it persisted on chelating cytosolic calcium. On the other hand, the released ATP activated purinergic receptors and mobilized intracellular calcium stores. The resulting depletion of stored calcium led to the activation of capacitative calcium entry. Increase in cytosolic calcium concentration was blocked by the purinergic receptor blocker suramin, phospholipase C inhibitor and apyrase, which hydrolyses ATP. Collectively, our data demonstrate that human keratinocytes are mechanically activated by hypo-osmotic shock, leading first to the release of ATP, which in turn stimulates purinergic receptors, resulting in the mobilization of intracellular calcium and capacitative calcium entry. These results emphasize the crucial role of ATP signalling in the transduction of mechanical stimuli in human keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / metabolism*
  • Adenosine Triphosphate / pharmacology
  • Calcium Channels / metabolism
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Gadolinium / pharmacology
  • Humans
  • Ion Channels / antagonists & inhibitors
  • Ion Channels / metabolism
  • Keratinocytes / drug effects
  • Keratinocytes / physiology*
  • Mechanotransduction, Cellular / drug effects
  • Mechanotransduction, Cellular / physiology*
  • Osmotic Pressure / physiology
  • Physical Stimulation
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Receptors, Purinergic P2Y / metabolism
  • Thapsigargin / pharmacology
  • Transient Receptor Potential Channels / agonists
  • Transient Receptor Potential Channels / metabolism
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism


  • 6-N,N-diethyl-beta,gamma-dibromomethylene-D-ATP
  • Calcium Channels
  • Chelating Agents
  • Ion Channels
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y
  • Transient Receptor Potential Channels
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Egtazic Acid
  • Thapsigargin
  • Adenosine Triphosphate
  • EGTA acetoxymethyl ester
  • Gadolinium
  • Type C Phospholipases
  • Adenosine Triphosphatases
  • ectoATPase