Depressed transient outward and calcium currents in dilated human atria

OBJECTIVE: The aim was to compare action potentials and ionic currents (steady state current, calcium current, calcium independent transient outward current) in two groups of trabeculae and myocytes, isolated from either dilated or non-dilated human atria. METHODS: Specimens of right atrial appendage were obtained from two groups of adult patients at the time of open heart surgery, a group with non-dilated atria and a group in which right atria were clearly dilated. Action potentials were recorded with standard microelectrodes from isolated superfused trabeculae. Action potentials and ionic currents were recorded from single myocytes using the patch clamp technique in the whole cell configuration in current clamp and voltage clamp modes respectively. RESULTS: In trabeculae taken from dilated atria the action potential was shortened and the plateau was markedly depressed compared to trabeculae taken from non-dilated atria. Similar results were obtained with single myocytes isolated from non-dilated and dilated atria. The density of the steady state current measured at the end of 0.75 s or 1 s pulses was not statistically different in the two groups of cells in the whole range of negative potentials, whereas at strongly positive potentials (> +40 mV) it was significantly reduced in cells from dilated atria compared to cells from non-dilated atria. The density of the total peak outward current was significantly reduced in cells from dilated atria 13.46(SEM 2.7) pA.pF-1 at +70 mV, n = 18 compared to cells from non-dilated atria 33.12(6.2) pA.pF-1, n = 20, p < 0.001. The transient component of outward current was strongly depressed (at +20 mV and more positive potentials) in cells from dilated atria. The calcium current density was still more severely depressed than the total outward current in cells from dilated atria 4.46(1.06) pA.pF-1 at +20 mV, n = 26 compared to cells from non-dilated atria 17.43(1.98) pA.pF-1, n = 38, p << 0.001. Kinetic parameters of both calcium and transient outward currents remained similar in cells from the two groups. CONCLUSIONS: The observation that in cells from dilated human atria the calcium current is more severely depressed than the total outward current can help to explain why in dilated human atria the action potential plateau is shorter and of lower amplitude than in non-dilated atria.