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

نویسندگان

  • Mingfeng Hu
  • Yuxia Liu
  • Jinzhi Wu
  • Xiaodong Liu
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Divergence in Endothelin-1- and Bradykinin-Activated Store-Operated Calcium Entry in Afferent Sensory Neurons

Endothelin-1 (ET-1) and bradykinin (BK) are endogenous peptides that signal through Gαq/11-protein coupled receptors (GPCRs) to produce nociceptor sensitization and pain. Both peptides activate phospholipase C to stimulate Ca(2+) accumulation, diacylglycerol production, and protein kinase C activation and are rapidly desensitized via a G-protein receptor kinase 2-dependent mechanism. However, E...

متن کامل

Transient receptor potential channels in cardiovascular function and disease.

Sustained elevation in the intracellular Ca2+ concentration via Ca2+ influx, which is activated by a variety of mechanisms, plays a central regulatory role for cardiovascular functions. Recent molecular biological research has disclosed an unexpectedly diverse array of Ca(2+-entry channel molecules involved in this Ca2+ influx. These include more than ten transient receptor potential (TRP) supe...

متن کامل

Recent Developments in Vascular Endothelial Cell TRP Channels Transient Receptor Potential Channels in Cardiovascular Function and Disease

Sustained elevation in the intracellular Ca concentration via Ca influx, which is activated by a variety of mechanisms, plays a central regulatory role for cardiovascular functions. Recent molecular biological research has disclosed an unexpectedly diverse array of Ca -entry channel molecules involved in this Ca influx. These include more than ten transient receptor potential (TRP) superfamily ...

متن کامل

Neuronal processing of noxious thermal stimuli mediated by dendritic Ca(2+) influx in Drosophila somatosensory neurons.

Adequate responses to noxious stimuli causing tissue damages are essential for organismal survival. Class IV neurons in Drosophila larvae are polymodal nociceptors responsible for thermal, mechanical, and light sensation. Importantly, activation of Class IV provoked distinct avoidance behaviors, depending on the inputs. We found that noxious thermal stimuli, but not blue light stimulation, caus...

متن کامل

Function and regulation of TRPP2 at the plasma membrane.

The vast majority (approximately 99%) of all known cases of autosomal dominant polycystic kidney disease (ADPKD) are caused by naturally occurring mutations in two separate, but genetically interacting, loci, pkd1 and pkd2. pkd1 encodes a large multispanning membrane protein (PKD1) of unknown function, while pkd2 encodes a protein (TRPP2, polycystin-2, or PKD2) of the transient receptor potenti...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cell reports

دوره 13 4  شماره 

صفحات  -

تاریخ انتشار 2015