The peptide CGRP increases a high-threshold Ca2+ current in rat nodose neurones via a pertussis toxin-sensitive pathway

Abstract

1. The whole-cell variation of the patch clamp technique was used to study the effect of calcitonin gene-related peptide (CGRP) on voltage-gated calcium currents in acutely dissociated rat nodose ganglion neurones and to determine if its effects were mediated via a guanine nucleotide binding (G) protein. 2. Both low- and high-threshold calcium current components were present in nodose ganglion neurones. CGRP had no effect on the isolated low-threshold current component. However, CGRP (1-1000 nM, ED50 = 50 nM) caused a concentration-dependent increase in high-threshold calcium currents. CGRP (1 microM) increased the peak of these calcium currents 21 +/- 4% over controls. 3. CGRP enhanced a transient high-threshold calcium current evoked from a holding potential of -80 mV but did not affect the slowly inactivating high-threshold current evoked from -40 mV. Multiple high-threshold calcium currents have been reported in sensory neurones. We cannot state unequivocally which high-threshold calcium current component was enhanced by CGRP. However, based on the observation that CGRP increased a transient but not the slowly inactivating high-threshold calcium current, we believe the peptide enhanced primarily the N-type calcium current component. 4. CGRP increased the maximal peak current and caused a modest negative shift of < or = 10 mV in the peak of the current-voltage (I-V) relation in three of six neurones. In the remaining three neurones the peptide increased the maximal peak current without a detectable shift in the peak of the I-V relation. 5. To determine if the CGRP-induced enhancement in calcium current was associated with an increase in calcium conductance, we studied the effect of the peptide on the instantaneous current-voltage (I-V) relation when currents were evoked at a clamp potential (Vc) of +30 mV, positive to the observed maximal current (Vc = 0 to +10 mV). CGRP increased the maximal conductance 23 +/- 4%. 6. The enhancement of calcium current by CGRP was not due to a shift in the voltage dependency of steady-state inactivation of the calcium channels. The stimulatory effect of CGRP on calcium current was evaluated by evoking currents from different holding potentials (Vh) at the same Vc (+10 mV). CGRP-induced increases in calcium currents were similar over the range of (Vh) from -60 to -110 mV, suggesting that the peptide did not alter voltage-dependent steady-state inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)