Omega-conotoxin CVID inhibits a pharmacologically distinct voltage-sensitive calcium channel associated with transmitter release from preganglionic nerve terminals.
Neurotransmitter release from preganglionic parasympathetic neurons is resistant to inhibition by selective antagonists of L-, N-, P/Q-, R-, and T-type calcium channels. In this study, the effects of different omega-conotoxins from genus Conus were investigated on current flow-through cloned voltage-sensitive calcium channels expressed in Xenopus oocytes and nerve-evoked transmitter release from the intact preganglionic cholinergic nerves innervating the rat submandibular ganglia. Our results indicate that omega-conotoxin CVID from Conus catus inhibits a pharmacologically distinct voltage-sensitive calcium channel involved in neurotransmitter release, whereas omega-conotoxin MVIIA had no effect. omega-Conotoxin CVID and MVIIA inhibited depolarization-activated Ba(2+) currents recorded from oocytes expressing N-type but not L- or R-type calcium channels. High affinity inhibition of the CVID-sensitive calcium channel was enhanced when position 10 of the omega-conotoxin was occupied by the smaller residue lysine as found in CVID instead of an arginine as found in MVIIA. Given that relatively small differences in the sequence of the N-type calcium channel alpha(1B) subunit can influence omega-conotoxin access (Feng, Z. P., Hamid, J., Doering, C., Bosey, G. M., Snutch, T. P., and Zamponi, G. W. (2001) J. Biol. Chem. 276, 15728-15735), it is likely that the calcium channel in preganglionic nerve terminals targeted by CVID is a N-type (Ca(v)2.2) calcium channel variant.
Adams
David J
DJ
School of Biomedical Sciences, The University of Queensland, Brisbane, Australia. dadams@mailbox.uq.edu.au
Smith
Amanda B
AB
Schroeder
Christina I
CI
Yasuda
Takahiro
T
Lewis
Richard J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials; D005724:Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011487:Protein Conformation; D051381:Rats; D014688:Venoms / Q000737:chemistry / Q000494:pharmacology*; D020960:omega-Conotoxins
C461486:AM336; D002121:Calcium Channel Blockers; D018377:Neurotransmitter Agents; D014688:Venoms; D020960:omega-Conotoxins