Channel blocking properties of a series of nicotinic cholinergic agonists.

Inhibition of the nicotinic acetylcholine receptor (nAChR) by channel blockade has been demonstrated with a variety of large organic cations, including several nicotinic agonists. We have studied the kinetics of channel blocking of a series of agonists which vary systematically in size and hydrophobicity due to a hydrocarbon chain from one to six carbons in length, as well as one agonist with a tertiary isomer of one hydrocarbon chain. Single-channel recording was used in combination with three different analysis techniques for determining the kinetic and equilibrium parameters of channel blockade. With an increasing number of methylenes, the blocking rates were essentially constant and the unblocking rates decreased exponentially. This is consistent with studies of the blocking properties of alcohols at the nAChR channel. Also, a linear decrease in the depth to which the larger agonists penetrate the membrane spanning region of the channel was observed. The three smaller agonists, however, all traverse approximately 75% of the membrane field, in agreement with previous measurements of the location of the narrowest region of the channel, the selectivity filter.

• Publication year

  1993

• Venue

  Biophysical Journal

• Publication date

  1993-08-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/S0006-3495(93)81103-2PMID 7693004PMCID PMC1225785
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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