Inward-rectifier K+ Current in Guinea-pig Ventricular Myocytes Exposed to Hyperosmotic Solutions

Abstract

Superfusion of heart cells with hyperosmotic solution causes cell shrinkage and inhibition of membrane ionic currents, including delayed-rectifer K+ currents. To determine whether osmotic shrinkage also inhibits inwardly-rectifying K+ current (I(K1)), guinea-pig ventricular myocytes in the perforated-patch or ruptured-patch configuration were superfused with a Tyrode's solution whose osmolarity (T) relative to isosmotic (1T) solution was increased to 1.3-2.2T by addition of sucrose. Hyperosmotic superfusate caused a rapid shrinkage that was accompanied by a negative shift in the reversal potential of Ba(2+)-sensitive I(K1), an increase in the amplitude of outward I(K1), and a steepening of the slope of the inward I(K1)-voltage (V) relation. The magnitude of these effects increased with external osmolarity. To evaluate the underlying changes in chord conductance (G(K1)) and rectification, G(K1)-V data were fitted with Boltzmann functions to determine maximal G(K1) (G(K1)max) and voltage at one-half G(K1)max (V(0.5)). Superfusion with hyperosmotic sucrose solutions led to significant increases in G(K1)max (e.g., 28 +/- 2% with 1.8T), and significant negative shifts in V(0.5) (e.g., -6.7 +/- 0.6 mV with 1.8T). Data from myocytes investigated under hyperosmotic conditions that do not induce shrinkage indicate that G(K1)max and V(0.5) were insensitive to hyperosmotic stress per se but sensitive to elevation of intracellular K+. We conclude that the effects of hyperosmotic sucrose solutions on I(K1) are related to shrinkage-induced concentrating of intracellular K+.

Osmolality- and Na+-dependent effects of hyperosmotic NaCl solution on contractile activity and Ca2+ cycling in rat ventricular myocytes

“…Increase in extracellular osmolality causes rapid loss of cell water, leading to a decrease in cell volume and an increase in the intracellular concentration of several solutes, including Na + [1,14,30,50]. In cardiac myocytes, cell shrinkage is not instantaneous but develops over 1-2 min and is not followed by regulatory volume increase up to 20 min of sustained hyperosmolality in the case of solutes with a high reflection coefficient, such as sucrose ( [35,38,50]; present results). Shrinkage of junctional SR, described in skeletal muscle fibers exposed to hyperosmotic sucrose solutions [17,33], might increase intra-SR [Ca 2+ ], even if the amount of Ca 2+ stored in the organelle is unaffected.…”

“…For each cell, the average of two repeated measures was taken at each time point, and cell volume was estimated as the product of cell length and the square of cell width, assuming proportional changes in cell width and thickness under hyperosmotic conditions [35]. In the presence of the NT solution, the estimated cell volume was 130±12 pl (N= 34).…”

Insensitivity of cardiac delayed‐rectifier IKr to tyrosine phosphorylation inhibitors and stimulators

“…The ‘true’ responses of whole‐cell I Kr to kinase modulators may be better preserved in myocytes investigated using the perforated‐patch technique than in those investigated using the ruptured‐patch technique (Heath & Terrar, 2000). To determine whether this was the case in the present study, we patched myocytes with pipettes that were filled with a nystatin solution (Korn & Horn, 1989; Missan et al ., 2004). The representative data and summary presented in Figure 3 indicate that the effects of 100 μ M concentrations of tyrphostin A23, tyrphostin A25, and genistein on I Kr in perforated‐patch myocytes were similar to those observed in ruptured‐patch myocytes.…”

Effects of Acute Hypernatremia on the Electrophysiology of Single Human Ventricular Cardiomyocytes: An In Silico Study

“…A reduction of 19 2% (mean SEM, n = 8) was also observed by Missan et al . [ 23 ], who also exposed isolated guinea pig ventricular cardiomyocytes to hyperosmotic Tyrode’s solution with a 1.5 times normal osmolarity. In isolated rat ventricular cardiomyocytes, 18% of the cell volume is osmotically inactive [ 24 ].…”

“…The available data on such direct functional effects of acute exposure to a hyperosmotic solution on individual ion currents, as obtained in isolated cardiomyocytes or an expression system, are summarized in Table 1 (Ref. [ 20 , 22 , 23 , 25 , 26 , 27 , 28 , 29 ]).…”