Effects of intracellular pH and Ca2+ on the activity of stretch-sensitive cation channels in leech neurons

Abstract

The effects of intracellular pH and calcium on the activity of the leech mechanosensitive cation channels have been studied. These channels exhibited two activity modes denoted as spike-like (SL) and multiconductance (MC). In the absence of mechanical stimulation, acidification of the intracellular side of membrane patches from 7.2 to 6.2 reversibly increased the mean channel open time as well as the opening frequency in the SL mode. Channels in MC mode were activated by a pH(i) reduction from 7.2 to 6.2, but were inhibited at pH(i) 5.5. Unlike MC mode, SL mode was strongly activated by intracellular Ca(2+). Fura-2 imaging experiments showed that intracellular calcium was induced to increase by hypotonic cell swelling. The major component of this response did not require extracellular calcium. A component of the swelling-induced calcium response was sensitive to blockers of stretch-sensitive cation channels. The results indicate that the two activity modes of mechanosensitive channels of leech neurons respond differently to changes of intracellular pH and calcium. The sensitivity of the channel to micromolar concentrations of internal free calcium, along with its permeability to this ion, is consistent with a role in the amplification of mechanically induced Ca(2+) signals in leech neurons.

Piezoelectric Nanoparticle-Assisted Wireless Neuronal Stimulation

“…The role of mechanosensitive channels in the low-amplitude and high-amplitude Ca 2+ transients respectively observed after the US and US + BTNP stimulations was investigated by perfoming Ca 2+ imaging experiments in the presence of 200 μM gentamicin, a blocker of mechano-sensitive cation channels that does not affect the voltage-gated Ca 2+ currents. − Even in the presence of gentamicin, low-amplitude (Δ F / F 0 peak = 0.15 ± 0.05) and high-amplitude (Δ F / F 0 peak = 0.78 ± 0.24; p < 0.05) Ca 2+ peaks were respectively detected after the US (Figure a) and the US + BTNP stimulations (Figure b), suggesting that the mechano-sensitive cation channels are not at the base of the mechanism describing the effects observed during the stimulations.…”

The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

“…Furthermore, stretch sensitivity is not a fixed channel property, but rather can undergo significant changes with changing extrinsic conditions. For example, mechanical and/or chemical disruption of the CSK can either enhance or abolish the stretch sensitivity of specific channels McBride 1992, 1997;Small and Morris 1994;Patel and Honoré 2001;; changes in bilayer thickness (Martinac and Hamill 2002), membrane voltage (Gu et al 2001;Morris and Juranka 2007), or dystrophin expression (Franco-Obregon and Lansman 2002) can switch specific MS channels between being stretch-activated to being stretch-inactivated; specific lipids (Patel and Honoré 2001;Chemin et al 2005), nucleotides (Barsanti et al 2006a, and references therein) and increased internal acidosis (Honoré et al 2002;Barsanti et al 2006b) can convert MS channels into constitutively open 'leak' channels. The basis for many of these changes involves changes in the way the bilayer, CSK and/or extracellular matrix conveys mechanical forces to the channel protein.…”