Reduction in external K causes increased action potential shortening in ventricular myocytes from the spontaneously hypertensive rat.
OBJECTIVE
(1) To study the effect of low external K and combined low K plus low Mg on the action potential of hypertrophied left ventricular myocytes isolated from the spontaneously hypertensive rat (SHR) and cells from normotensive control rats (NCR). (2) To identify differences in the response of SHR and NCR ventricular myocytes to low K and low K plus low Mg that could contribute to the increased number of arrhythmias observed in hypertrophied hearts.


METHODS
Cells were superfused with Tyrode's solution containing 6 mmol/l K and stimulated at 1 Hz. Action potentials were recorded using the patch clamp technique. The effect of low K (2.4 mmol/l) and combined low K plus low Mg (2.4 mmol/l K and nominally zero Mg) on the characteristics of the action potential was measured in nine SHR, eight Wistar-Kyoto rat and 5 Wistar rat cells.


RESULTS
With 6 mmol/l K, the action potential was prolonged significantly in SHR cells at 50, 70, 90 and 95% repolarizations. Both low K and low K plus low Mg shortened the action potential significantly only at 70% repolarization in NCR cells. In contrast, both low K and low K plus Mg led to marked action potential shortening at 70 and 90% repolarizations in SHR cells (P < 0.01) and also at 50 and 95% repolarizations (P < 0.05). Combined low K plus low Mg produced no additional effect on the action potential shape either in SHR or in NCR cells compared with that produced by low K alone. Although in SHR cells low K and combined low K plus low Mg produced a greater shortening of the action potential, which extended across a longer period of repolarization, a significant prolongation of the action potential still remained with low K at 50 and 95% repolarizations in SHR cells compared with that in NCR cells.


CONCLUSIONS
Low K shortened the action potential both in NCR and in SHR cells but had a much greater effect on the action potential shape in SHR cells. Low K attenuated the difference in action potential shape between SHR and NCR by reducing the longer plateau observed in SHR cells. Combined low K plus low Mg exerted an effect on the action potential shape similar to that of low K alone in all cells. This increased shortening of the action potential produced by low K in SHR cells might be relevant to the increased incidence of arrhythmias associated with left ventricular hypertrophy, perhaps by shortening the wavelength of excitation and encouraging re-entrant arrhythmias, or by increasing the heterogeneity of repolarization within the ventricle.
Evans
S J
SJ
Department of Cardiology, School of Medical Sciences, University of Bristol, UK.
Jones
J V
JV
Levi
A J
AJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D006332:Cardiomegaly / Q000503:physiopathology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000473:pathology; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar
D008274:Magnesium; D011188:Potassium