Charybdotoxin block of Ca(2+)-activated K+ channels in colonic muscle depends on membrane potential dynamics

The American Journal of Physiology
B W FreyN G Publicover

Abstract

Charybdotoxin (ChTX) is a specific blocker of Ca(2+)-activated K+ channels. The voltage- and time-dependent dynamics of ChTX block were investigated using canine colonic myocytes and the whole cell patch-clamp technique with step and ramp depolarization protocols. During prolonged step depolarizations, K+ current slowly increased in the continued presence of ChTX (100 nM). The rate of increase depended on membrane potential with an e-fold change for every 60 mV. During ramp depolarizations, the effectiveness of ChTX block depended significantly on the rate of the ramp (50% at 0.01 V/s to 80% at 0.5 V/s). Results are consistent with a mechanism in which ChTX slowly "unbinds" in a voltage-dependent manner. A simple kinetic model was developed in which ChTX binds to both open and closed states. Slow unbinding is consistent with ChTX having little effect on electrical slow waves recorded from circular muscle while causing depolarization and contraction of longitudinal muscle, which displays more rapid "spikes." Resting membrane potential and membrane potential dynamics are important determinants of ChTX action.

References

Jul 1, 1992·The American Journal of Physiology·K D ThornburyK M Sanders
Jan 1, 1992·Annual Review of Physiology·K M Sanders
Aug 1, 1990·Journal of Neuroscience Methods·A Carl, K M Sanders
Sep 1, 1989·The American Journal of Physiology·A Carl, K M Sanders
Aug 1, 1986·The Journal of Physiology·K M Sanders, T K Smith
Feb 1, 1987·The American Journal of Physiology·T K SmithK M Sanders
Mar 1, 1987·The American Journal of Physiology·T K SmithK M Sanders
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Nov 1, 1983·The Journal of Physiology·K L Magleby, B S Pallotta
Sep 1, 1983·The Journal of Physiology·T Y El-Sharkawy
Dec 1, 1994·The American Journal of Physiology·K SatoN G Publicover
May 1, 1996·The American Journal of Physiology·E P BurkeN G Publicover
Mar 3, 1949·The Journal of Physiology·A L HODGKIN, B KATZ

❮ Previous
Next ❯

Citations

Oct 20, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·F M Faraci, C G Sobey
Apr 9, 2001·Antioxidants & Redox Signaling·V R Muzykantov
Apr 30, 1999·Physiological Reviews·M J Davis, M A Hill
Dec 22, 2007·The Journal of Physiological Sciences : JPS·Hui-Shu GuoQing-Hui Qi
Jan 27, 2009·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Anne PrévotDolores Mosig
Aug 17, 1999·The Journal of Clinical Investigation·S A LitherlandM J Clare-Salzler
May 17, 2007·Molecular Biology Reports·Xiongfei ZhangXiao Han
Jul 10, 2007·Journal of Physiology and Biochemistry·V LamarcaM D Murillo
Feb 15, 2013·American Journal of Physiology. Cell Physiology·Colin J StonekingMichael J Mason
Jun 24, 2004·The Journal of Biological Chemistry·Fan Yang, David Bleich

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.