Abstract:
The membrane properties of isolated frog parathyroid
cells were studied using perforated and conventional
whole-cell patch-clamp techniques. Frog parathyroid cells
displayed transient inward currents in response to
depolarizing pulses from a holding potential of –84·mV.
We analyzed the biophysical properties of the inward
currents. The inward currents disappeared by the
replacement of external Na+ with NMDG+ and were
reversibly inhibited by 3· mol·l
–1 TTX, indicating that the
currents occur through the TTX-sensitive voltage-gated
Na+ channels. Current density elicited by a voltage step
from –84·mV to –24·mV was –80·pA·pF–1 in perforated
mode and –55·pA·pF–1 in conventional mode. Current
density was decreased to –12·pA·pF–1 by internal GTP S
(0.5·mmol·l
–1), but not affected by internal GDP S
(1·mmol·l
-1). The voltage of half-maximum (V1/2)
activation was –46·mV in both perforated and
conventional modes. V1/2 of inactivation was –80·mV in
perforated mode and –86·mV in conventional mode.
Internal GTP S (0.5·mmol·l
–1) shifted the V1/2 for
activation to –36·mV and for inactivation to –98·mV. A
putative endocannabinoid, 2-arachidonoylglycerol ether
(2-AG ether, 50· mol·l
–1) and a cannabinomimetic
aminoalkylindole, WIN 55,212-2 (10· mol·l
–1) also greatly
reduced the Na+ current and shifted the V1/2 for activation
and inactivation. The results suggest that the Na+ currents
in frog parathyroid cells can be modulated by
cannabinoids via a G protein-dependent mechanism.