The Effects of K+ Channels Modulators Terikalant and Glibenclamide on Membrane Potential Changes Induced by Hypotonic Challenge of Guinea Pig Ventricular Myocytes

Abstract

Abstract. Contribution of inward rectifier K+ currents (I K1 ) and ATP-sensitive K + currents (I KATP ) to membrane potential changes of ventricular myocytes appearing during hypotonic challenge is unclear. We used here the whole cell patch clamp technique, voltage and current clamp modes, to record membrane potentials and ionic currents in isolated guinea pig ventricular myocytes under isotonic or hypotonic perfusion. The difference in osmolarity between isoand hypotonic solutions was about 100 mOsm. Exposure to hypotonic solution for 60 s induced initial prolongation of action potential duration at 90% of repolarization (APD 90 ) (from 176 ± 10 to 189 ± 11 ms, P<0.05, n = 13). Further perfusion for the next 300 s shorthened APD 90 to 135 ± 9 ms (P<0.01, in comparison with control values, n = 13) and depolarized resting potential from -79.2 ± 1.5 to -75.0 ± 0.9 mV, (P<0.05, n = 13). Neither pretreatment with a blocker of I K1 channels, terikalant at 10 m M, nor with a blocker of I KATP channels, glibenclamide at 1 m M, prevented the above-mentioned changes in membrane potential induced by hypotonic challenge when a pipette solution containing 5 mM ATP was used. Also, glibenclamide and terikalant did not affect the hypotonic-sensitive current, obtained by ramp or voltage-step protocols, respectively. Additionally, the current-voltage relationship (I-V curve) of the whole cell hypotonic-sensitive current shifted from an isotonic I-V curve in a parallel way. Our results indicate that I K1 and I KATP do not participate in membrane potential changes induced by hypotonic solution at least in the guinea pig ventricular myocytes with sufficient intracellular ATP.

Involvement of the phosphatidylinositol kinase pathway in augmentation of ATP-sensitive K+ channel currents by hypo-osmotic stress in rat ventricular myocytes

“…On the other hand, hypo-osmotic stress increased efficacy of K + -channel opening drugs to activate I K,ATP in guinea-pig ventricular myocytes (Kocic et al 2007). These findings by Kocic et al (2004a; are in agreement with our observations of rat ventricular myocytes in terms of (1) lack…”

“…This abbreviation of APD was associated with appearance of outward currents that were inhibited by glibenclamide, a blocker of K ATP channels (Priebe and Beuckelmann 1998). In contrast, it was reported that, using terikalant (a blocker of inward rectifier K + currents (I K1 )) and glibenclamide, neither I K1 nor I K,ATP participated in membrane potential changes induced by hypo-osmotic solution at least with sufficient intracellular ATP (Kocic et al 2004a). On the other hand, hypo-osmotic stress increased efficacy of K + -channel opening drugs to activate I K,ATP in guinea-pig ventricular myocytes (Kocic et al 2007).…”

“…It was reported that hypo-osmotic cell swelling increased the Cl -channel currents (I Cl ), delayed rectifier K + currents (I Ks ), non-selective cation current, Na-K pump current, and I K,ATP in cardiac myocytes (Sasaki et al 1994;Zhou et al 1997;Priebe and Beuckelmann 1998;Bewick et al 1999;Kocic et al 2001;Kocic et al 2004a;Kocic et al 2004b;Kocic et al 2007;Ren et al 2008;Piron et al 2010). Several mechanisms have been proposed for the hypo-osmotic stimulation of these ionic conductance including the activation of tyrosine kinase, phophatidylinositol 3-kinase (PI-3K) and a serine/threonine protein phosphatase, and the interaction with actin filaments (Zhou et al 1997;;Bewick et al 1999;Kocic et al 2004b;Ren et al 2008;Piron et al 2010).…”

Muscle KATPChannels: Recent Insights to Energy Sensing and Myoprotection

“…The functional implication of disparate structure of atrial and ventricular K ATP is unclear, but conceivably, SUR1-based channels are necessary for an atrial specific function, such as coupling atrial stretch with the secretion of atrial natriuretic peptide (186, 206, 348, 441). Interestingly, atrial K ATP channels have been reported to be activated by stretch (214, 326, 416), although the data is sparse, and the finding that atrial Kir3.4 channels are also stretch-sensitive (173) may provide an alternative explanation.…”

Modulators of Ion Channels Activated by Hypotonic Swelling in Cardiomyocytes: New Perspectives for Pharmacological Treatment of Life-Threatening Arrhythmias

“…Some authors claimed that I KATP are activated during cell swelling, but only at low concentration of ATP in the cell [44,45]. On the other hand, in the presence of 5 mM of ATP in the pipette solution, no I KATP was detected during hypotonic swelling of guinea pig ventricular myocytes [13,46]. But, it is clear that neither activation nor inhibition of these channels has significant influence on the cardiac cell volume.…”