Effects of ATP-regulated potassium channels modulators, N-(2-pyridyl)-N'-(4-toluol) sulfonylcarbamides, on electromechanical activity in guinea pig myocardium

Vida Gendvilienė, Danguolė Zablockaitė, Herta Gurskaitė, Irma Martišienė, Antanas Stankevičius

Institute of Cardiology, Kaunas University of Medicine, Lithuania

Key words: papillary muscle of guinea pig, pinacidil, 2-aminopyridine, sulfonylcarbamide derivatives of 2-aminopyridine, action potential duration, contraction force.

Summary. The aim of the study was to investigate the effects of 2-aminopyridine (2-AP) and its new sulfonylcarbamide derivatives AP21, AP22, AP26, and AP27 (10^–5–10^–3 M) on pinacidil (5×10^–5 M), an activator of K_ATP channels, induced shortening of action potential duration and reduction of contraction force in guinea pig papillary muscles. Experiments were carried out using a standard method of myocardium electromechanical activity registration. Under control conditions (perfusion of papillary muscles with Tyrode solution), an average of action potential duration (APD), measured at 90% (APD₉₀) and 50% (APD₅₀) of repolarization, were 211.78±8.6 ms and 173.22±8.3 ms (n=18), respectively, and contraction force was 1.77±0.36 mN (n=18). Pinacidil markedly decreased APD₉₀ to 58.16±4.4%, APD₅₀ – to 52.51±4.85% (n=18), and contraction force – to 30.45±4.06% (n=18), (p<0.001) vs. control.

2-aminopyridine and its sulfonylcarbamide derivative AP22 (with 4-toluolsulfonylcarbamide fragment and methyl iodide-quaternized nitrogen of the pyridine ring) had no effect on the pinacidil-induced shortening of action potential and reduction of contraction force. 2-aminopyridine derivatives, AP21 (with 4-toluolsulfonylcarbamide fragment) and AP26 (with allyl bromide-quaternized nitrogen of the pyridine ring), showed a weak effect on pinacidil-induced shortening of action potential duration. The 2-aminopyridine derivative AP27 (with the 4-toluolsulfonylcarbamide fragment where nitrogen of the pyridine ring was quaternized by 4-nitrobenzyl bromide) had the most potent stimulatory effect on action potential duration and contraction force, which were reduced by pinacidil.

Correspondence to V. Gendvilienė, Institute of Cardiology, Kaunas University of Medicine, Sukilėlių 17, 50161 Kaunas, Lithuania. E-mail: membiof@kmu.lt

Received 18 May 2006, accepted 17 August 2006