Ca(2+)-induced Ca(2+) release in sensory neurons: low gain amplification confers intrinsic stability.
Ca(2+)-induced Ca(2+) release (CICR) is a ubiquitous mechanism by which Ca(2+) release from the endoplasmic reticulum amplifies the trigger Ca(2+) entry and generates propagating Ca(2+) waves. To elucidate the mechanisms that control this positive feedback, we investigated the spatial and temporal kinetics and measured the gain function of CICR in small sensory neurons from mammalian dorsal root ganglions (DRGs). We found that subsurface Ca(2+) release units (CRUs) are under tight local control by Ca(2+) entry, whereas medullar CRUs as a "common pool" system are recruited by inwardly propagating CICR. Active CRUs often displayed repetitive Ca(2+) sparks, conferring the ability to encode a "memory" of neuronal activity well beyond the duration of an action potential. Store Ca(2+) reserve was able to support all CRUs each to fire approximately 15 sparks, excluding use-dependent inactivation or store depletion as the major CICR termination mechanism. Importantly, CICR in DRG neurons operated in a low gain, linear regime (gain = 0.54), which conferred intrinsic stability to CICR. Combined with high Ca(2+) current density (-156 pA/pF at -10 mV), such a low gain CICR system generated large intracellular Ca(2+) transients without jeopardizing the stability. These findings provide the first demonstration that CICR operating in a low gain regime can be harnessed to provide a robust and graded amplification of Ca(2+) signal in the absence of counteracting inhibitory mechanism.
Ouyang
Kunfu
K
Institute of Molecualr Medicine and National Laboratory of Biomembrane and Membrane Biotechnology, College of Life Science, Peking University, Beijing 100871, China.
Wu
Caihong
C
Cheng
Heping
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D002118:Calcium