PT  - JOURNAL ARTICLE
AU  - Makoto Okazawa
AU  - Keizo Takao
AU  - Aiko Hori
AU  - Takuma Shiraki
AU  - Kiyoshi Matsumura
AU  - Shigeo Kobayashi
TI  - Ionic Basis of Cold Receptors Acting as Thermostats
AID  - 10.1523/JNEUROSCI.22-10-03994.2002
DP  - 2002 May 15
TA  - The Journal of Neuroscience
PG  - 3994--4001
VI  - 22
IP  - 10
4099  - http://www.jneurosci.org/content/22/10/3994.short
4100  - http://www.jneurosci.org/content/22/10/3994.full
SO  - J. Neurosci.2002 May 15; 22
AB  - When temperature (T) of skin decreases stepwise, cold fibers evoke transient afferent discharges, inducing cold sensation and heat-gain responses. Hence we have proposed that cold receptors at distal ends of cold fibers are thermostats to regulate skin T against cold. Here, with patch-clamp techniques, we studied the ionic basis of cold receptors in cultured dorsal root ganglion (DRG) neurons of rats, as a model of nerve endings. Cells that increased cytosolic Ca2+ level in response to moderate cooling were identified as neurons with cold receptors. In whole-cell current-clamp recordings of these cells, in response to cooling, cold receptors evoked a dynamic receptor potential (RP), eliciting impulses briefly. In voltage-clamp recordings (-60 mV), step cooling induced an inward cold current (Icold) with inactivation, underlying the dynamic RP. Ca2+ ions that entered into cells from extracellular side induced the inactivation. Analysis of the reversal potential implied thatIcold was nonselective cation current with high Ca2+ permeability. Threshold temperatures of cooling-induced Ca2+ response andIcold were different primarily among cells. In outside-out patches, when T decreased, single nonselective cation channels became active at a critical T. This implies that a cold receptor is an ion channel and acts as the smallest thermostat. Because these thermal properties were consistent with that in cold fibers, we conclude that the same cold receptors exist at nerve endings and generate afferent impulses for cold sensation and heat-gain behaviors in response to cold.