Effects of aluminium on electrical and mechanical properties of frog atrial muscle

Abstract

The effects of aluminium on membrane ionic currents were studied in single cardiac myocytes. Most of the work was done on frog atrial cells, but some experiments were also carried out on single cells isolated from rabbit ventricles and atria. The effects of aluminium on the force of contraction of frog atrial trabeculae were also investigated. Aluminium was prepared from AlCl3 as a stock 0.5 m solution which has a pH of 3.5. Before each experiment, this solution was added to the control solution, to give a final concentration of 20–100 μg ml−1 aluminium (0.75–3.75 mm AlCl3). The solutions were brought to a pH of 7.4 or 7.6, at which they consist of a mixture of amorphous aluminium hydroxides and a very small amount of soluble ionic aluminium complexes: free aluminium cations (less than 10 pm), aluminohydroxide anions (less than 8 μm). The addition of this suspension reduced the peak inward calcium currents in single rabbit atrial and ventricular cells and in frog atrial cells. In the latter, the peak current was reduced (at + 10 mV) to 45% of control (mean of 9 cells). This effect was reversible upon washout, and was obtained at all membrane potentials, with no shift of the calcium current voltage relationship along the voltage axis. Aluminium also reduced the time‐dependent potassium current IK. This reduction was observed at all membrane potentials. For example, at + 10 mV, the mean reduction of IK (n = 9) was to 69% of the control amplitude. This effect, which was very difficult to reverse, was not due to IK rundown. The fully activated current‐voltage relationships (obtained by standard ‘tail’ analysis) showed that the effect of aluminium was due mainly to a decrease in conductance and not to a shift in the activation range of IK. The mean voltage of half activation was shifted by 8 mV in the depolarizing direction (n = 5). The background potassium current IK1 was also slightly but consistently changed in a complex fashion, with an outward shift at membrane potentials positive to −60 mV. For example, at a membrane potential of −40 mV, the mean shift was by 22 ± 4 pA. At more negative potentials, there was an inward shift in the current amplitudes. For example, for steps to −100 mV the current elicited was larger (more inward) by 53 pA (mean value, n = 10). The reversal potential was slightly shifted (< 10 mV) in the hyperpolarizing direction. The force of contraction of frog atrial trabeculae was altered by aluminium in a complex manner, which showed marked seasonal variation. During most of the year, 50–100 μg ml−1 aluminium caused a biphasic change, with an early small and consistent decrease, followed by a large increase in twitch amplitude. For a short period corresponding to the (local) winter months the sensitivity to aluminium was greatly enhanced. Aluminium 100 μg ml−1 totally abolished contraction (n = 5), while a lower concentration (20 μg ml−1) produced a sustained reduction in the force of contraction. Similar biphasic and seasonal responses have been reported to be induced by lanthanum. The biph...

Aluminum(III) Interactions with the Acidic Amino Acid Chains

“…In addition to magnesium(II), iron(III) 12 and calcium(II) [13][14][15] are also susceptible to competition with aluminum(III). Size similarity is a dominant factor over the charge identity concerning metal ion competition.…”

“…In addition to magnesium(II), iron(III) and calcium(II) − are also susceptible to competition with aluminum(III). Size similarity is a dominant factor over the charge identity concerning metal ion competition. , Thus, aluminum(III) substitution for magnesium(II), calcium(II), or iron(III) in physiological settings is possible.…”

Aluminium alters excitability by inhibiting calcium, sodium and potassium currents in bovine chromaffin cells

“…It has been reported that Al 3+ binds to calcium channels (Busselbert et al, 1994) modulating the amplitude of excitatory post-synaptic potentials (Platt and Büsselberg, 1994;Platt et al, 1995); while its effects on other ionic currents are less remarkable (Meiri and Shimoni, 1991).…”

“…currents (Meiri and Shimoni, 1991;Platt and Büsselberg, 1994) while high levels of Al 3+ increase these conductance (Chen et al, 2005). It seems that Al 3+ may binding to at least three different specific binding sites in calcium channels, generating a selective effect on calcium channels, with less action on voltage-activated sodium and potassium channel currents (Busselberg et al, 1994).…”

“…Low levels of Al 3+ have been reported to inhibit calcium currents (Busselberg et al, 2009; Platt and Busselberg, 1994), reducing the amplitude of excitatory postsynaptic potentials (EPSP) (Platt et al, 1995); while higher levels improve calcium currents (Chen et al, 2005), increasing the amplitude of the EPSPs (Platt et al, 1995). While its effects on other ionic currents, such as sodium and potassium currents, seem to be scarce (Meiri and Shimoni, 1991). This metal has been reported to alter long-term potentiation (LTP) (Song et al, 2014), the neurophysiology basis of learning and memory (Wang et al, 2010; Cao et al, 2016); processes where Ca 2+ /calmodulin-dependent protein kinase II and cAMP-dependent protein kinases are important (Harris et al, 1994; Frey et al, 1993; Malenka et al, 1989, Matthis et al, 1993).…”