Influx-Operated Ca(2+) Entry via PKD2-L1 and PKD1-L3 Channels Facilitates Sensory Responses to Polymodal Transient Stimuli

Cell Rep. 2015 Oct 27;13(4):798-811. doi: 10.1016/j.celrep.2015.09.041. Epub 2015 Oct 17.

Abstract

The polycystic TRP subfamily member PKD2-L1, in complex with PKD1-L3, is involved in physiological responses to diverse stimuli. A major challenge to understanding whether and how PKD2-L1/PKD1-L3 acts as a bona fide molecular transducer is that recombinant channels usually respond with small or undetectable currents. Here, we discover a type of Ca(2+) influx-operated Ca(2+) entry (ICE) that generates pronounced Ca(2+) spikes. Triggered by rapid onset/offset of Ca(2+), voltage, or acid stimuli, Ca(2+)-dependent activation amplifies a small Ca(2+) influx via the channel. Ca(2+) concurrently drives a self-limiting negative feedback (Ca(2+)-dependent inactivation) that is regulated by the Ca(2+)-binding EF hands of PKD2-L1. Our results suggest a biphasic ICE with opposite Ca(2+) feedback regulation that facilitates sensory responses to multimodal transient stimuli. We suggest that such a mechanism may also occur for other sensory modalities and other Ca(2+) channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology
  • Cell Line
  • Cricetulus
  • Electrophysiology
  • Humans
  • Mice
  • Receptors, Cell Surface / metabolism*
  • TRPP Cation Channels / metabolism*

Substances

  • Calcium Channels
  • PKD1L3 protein, mouse
  • Pkd2l1 protein, mouse
  • Receptors, Cell Surface
  • TRPP Cation Channels
  • Calcium