Calcium-sensitive delayed rectifier potassium current in guinea pig ventricular cells

Abstract

The calcium sensitivity of the delayed rectifier K+ current (IK) was investigated in guinea pig single ventricular cells using the whole cell configuration of the patch-clamp technique with a cell dialysis method. The concentration-response curve of IK for intracellular Ca2+ indicated that IK started to increase at intracellular Ca2+ concentration [Ca2+]i of 10(-8) M (pCa 8) and it increased threefold at pCa 7. At lower [Ca2+]i than pCa 9, IK remained unchanged. A shift of the activation curve of IK by the elevation of [Ca2+]i was not observed. Although [Ca2+]i had little effect on time constants of the activation and deactivation of IK, it predominantly increased the amplitudes of the fast components in the activation process and the slow component in the deactivation process. In the ensemble noise analysis, the elevation of [Ca2+]i increased the number and open probability of functional IK channels but not the unit amplitude of IK channel. These results suggest that the elevation of [Ca2+]i enhances IK, probably by increasing the number and open probability of functional IK channels. Ca2(+)-sensitive IK in cardiac cells is a class of current different from Ca2(+)-activated K+ current in other tissue because the activation curve of Ca2(+)-sensitive IK was not shifted by the [Ca2+]i elevation, and the single channel conductance of IK was smaller than the one of Ca2(+)-activated K+ current.

Enhancement of delayed rectifier K+ current by P2‐purinoceptor stimulation in guinea‐pig atrial cells.

“…7), indicating that the stimulatory effect of ATP on IK was not obligatorily dependent upon intracellular Ca2+. The deactivation time course of IK has been shown to be slowed by the elevation of intracellular Ca2P (Tohse et al 1987;Tohse, 1990), whereas the present investigation demonstrates that extracellular ATP or ADP increased IK without significantly changing the current kinetics (Figs 3 and 4). This finding may also support our view that intracellular Ca2+ does not mediate the IK response to ATP.…”

“…Both an elevation in intracellular free Ca2+ (Tohse et al 1987;Tohse, 1990) and an activation of protein kinase C (Tohse et al 1987;Walsh & Kass, 1988) The peak amplitude of the 'K tail current was measured on return to a holding potential of -40 mV after a 500 ms voltage step to +40 mV with various concentrations of ATP (0) the IK tail current elicited on return to the holding potential (-40 mV) from +40 mV by 39-6 + 8-9 %, which was similar to the enhancement observed in cells loaded with 5 mm EGTA (48-0 + 7.9%, n = 7), showing that the stimulatory effect of ATP on IK was not affected by an increased Ca2P-buffering capacity achieved by BAPTA.…”

“…In various types of cardiac cells, IK has been demonstrated to be regulated by protein kinase A (see Introduction in Yazawa & Kameyama, 1990), protein kinase C (Tohse et al 1987;Walsh & Kass, 1988) and intracellular Ca2+ (>10-8 M) (Tohse et al 1987;Tohse, 1990). In our study, the stimulatory effect of extracellular ATP on IK was found to be additive to that of maximally effective concentrations (0 5-1P0 FM) of isoprenaline (Fig.…”

“…This finding may also support our view that intracellular Ca2+ does not mediate the IK response to ATP. In guinea-pig ventricular myocytes, IK is known to be regulated by intracellular Ca2P concentrations greater than 10 8 M (Tohse et al 1987;Tohse, 1990 heart, P2-purinoceptor stimulation has been demonstrated to stimulate arachidonic acid metabolism through cyclooxygenase and, thereby, produce prostaglandins (Takikawa et al 1990). It remains to be elucidated whether such pathways are involved in the intracellular mechanism mediating the P2-purinergic regulation of IK.…”

“…In pacemaker cells the deactivation of IK has been regarded as one of the major factors contributing to the development of pacemaker depolarization (for review see Irisawa, 1978). This important K+ current system has been shown to be Fegulated by several mechanisms, such as protein kinase A (for references see Yazawa & Kameyama, 1990), protein kinase C (Tohse, Kameyama & Irisawa, 1987;Walsh & Kass, 1988) and intracellular Ca2+ (Tohse et al 1987;Tohse, 1990). Here we report that stimulation of P2-purinoceptors in atrial cells potentiates IK through intracellular steps that appear to be independent of protein kinase A, protein kinase C and intracellular Ca2+.…”