Related Experiment Video
Updated: Aug 11, 2026

Double-barreled and Concentric Microelectrodes for Measurement of Extracellular Ion Signals in Brain Tissue
Published on: September 5, 2015
Inhibition of slow-wave repolarization and Ca(2+)-activated K+ channels by quaternary ammonium ions
1Department of Physiology, University of Nevada School of Medicine, Reno 89557-0046.
Abstract:
We studied the effects of the K+ channel blocker tetrapentylammonium (TPeA) on the electrical activity of intact circular smooth muscle from canine colon. TPeA (10 and 20 microM) increased slow-wave duration and "locked" the membrane potential around -30 mV plateau potential after several minutes of application, suggesting that K+ channels are essential for termination of colonic slow waves. Repolarization and normal slow-wave activity resumed after 20-30 min of washout. The patch-clamp technique was used to study the block of large-conductance Ca(2+)-activated K+ channels (BK channels) by TPeA and tetraethylammonium (TEA) in excised and cell-attached patches from isolated colonic smooth muscle cells. Channel block was characterized by a voltage-dependent dissociation constant [Kd(V)] for the binding of TEA and TPeA to a blocking site located a fraction of the distance across the membrane field (delta). The extracellular TEA binding site had a Kd(0) of 0.33 mM and a delta of 0.23. The extracellular TPeA binding site had a Kd(0) of 2.2 mM but showed significantly less voltage dependence (delta = 0.02). The intracellular binding site for TEA was of low affinity [Kd(0) = 76 mM]. Intracellular TPeA was the most potent blocker of BK channel current [Kd(0) = 11.7 microM]. The voltage dependence of block by intracellular TPeA (delta = -0.21) was not significantly different from that of intracellular TEA (delta = -0.3). Internal TPeA (10 microM) also blocked a 70-pS K+ channel and a 23-pS K+ channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Tetrapentylammonium (TPeA) prolongs colonic smooth muscle slow waves by blocking potassium channels. Intracellular TPeA is a potent blocker of large-conductance calcium-activated potassium (BK) channels, essential for repolarization.
Area of Science:
- Physiology
- Pharmacology
- Ion Channel Biology
Background:
- Potassium (K+) channels play a crucial role in regulating smooth muscle electrical activity.
- Understanding K+ channel function is vital for elucidating mechanisms of gastrointestinal motility.
Purpose of the Study:
- To investigate the effects of the K+ channel blocker tetrapentylammonium (TPeA) on canine colonic smooth muscle electrical activity.
- To characterize the block of large-conductance calcium-activated potassium (BK) channels by TPeA and tetraethylammonium (TEA) using the patch-clamp technique.
Main Methods:
- Studied intact circular smooth muscle from canine colon.
- Utilized the patch-clamp technique on excised and cell-attached patches from isolated colonic smooth muscle cells.
- Characterized voltage-dependent binding kinetics of TPeA and TEA to BK channels.
Main Results:
- TPeA (10 and 20 microM) increased slow-wave duration and plateau potential, indicating K+ channels are essential for terminating colonic slow waves.
- Intracellular TPeA was a potent blocker of BK channel current (Kd(0) = 11.7 microM) with significant voltage dependence.
- TPeA also blocked other K+ channels, including 70-pS and 23-pS channels.
Conclusions:
- K+ channels are critical for the repolarization phase of colonic smooth muscle slow waves.
- TPeA effectively blocks BK channels, particularly from the intracellular side, impacting colonic electrical activity.
- TPeA serves as a valuable tool for studying K+ channel function in smooth muscle physiology.
Related Concept Videos
The Role of Ion Channels in Neuronal Computation
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential.
Voltage-gated Ion Channels
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Antihypertensive Drugs: Action of Calcium Channel Blockers
Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers
Class 1A Antiarrhythmic Drugs: These drugs work by moderately blocking sodium channels,...
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

