Functional Evidence for Intracellular Acid Extruders in Human Ventricular Myocardium.

Abstract

The ability to maintain optimal intracellular pH (pH i )is an essential requirement for all cells. A wealth of biological processes have been found to be sensitive to changes in pH i . These include enzyme activity [1], control of the cell volume [2], the regulation of cellular growth and differentiation [3], and the kinetic properties of Na ϩ , K ϩ , and Ca 2ϩ channels [4]. The pH i regulatory mechanism is especially important for the heart, since changes in pH i dramatically affect contractility and rhythm [5][6][7]. Moreover, it has been demonstrated that during myocardial ischemia, the pH i is substantially lowered [8], but during postischemia reperfusion, a rapid recovery of the pH i is observed [9]. Therefore these pH i disturbances have been claimed to be responsible for the reversible contractile dysfunction and malignant ventricular arrhythmias seen in cardiac myocytes [9].In animal cardiac cells, remarkable progress has been made in understanding the pH i regulating system over the past decade. It is well known now that the pH i in animal cardiac cells is kept within a narrow range (7.0-7.2) by a combination of active sarcolemmal transporters, i.e., intracellular acid-extrusion and acidloading carriers, and the passive intracellular buffering capacity [10, 11]. Na ϩ -H ϩ exchange (NHE) is important for pH i control in the animal heart, being one

Sarcolemmal localisation of Na+/H+ exchange and Na+–HCO3− co‐transport influences the spatial regulation of intracellular pH in rat ventricular myocytes

“…In contrast, because of the lack of NHE1 activity in t‐tubules, acid extrusion in these latter regions is dependent on HCO 3 − ion influx via NBC. A comparable spatial pattern for ventricular NHE1 and NBC is likely to operate in other mammalian species, including human, given that the same component transporters have been identified (Leem et al 1999; Yokoyama et al 2000; Loh et al 2002; Yamamoto et al 2005). Indeed, in guinea‐pig ventricular myocytes, we have observed universal sarcolemmal immunofluorescence for NBCe1 (including t‐tubules and intercalated discs; n = 14), but no reduction of NHE1‐mediated acid extrusion after detubulation (pH i epifluorescence experiments, n = 5), identical to the situation in rat myocytes.…”

Expressional and Functional Characterization of Intracellular pH Regulators and Effects of Ethanol in Human Oral Epidermoid Carcinoma Cells

“…NHE is an electroneutral housekeeping transporter that mediates the exchange of [ [15,25,26]. Under HEPES-buffered media (HCO 3 --free), the pH i recovery from acidification through NHE can be inhibited by removal of [Na + ] o or by the addition of a specific and potent NHE1 inhibitor, such as Hoe 694 [26,27]. However, in CO 2 /HCO 3 -buffered Tyrode solution, NBC coexists with NHE to achieve acid-equivalent extrusion in many mammalian cells [24,25,27,28].…”

“…Under HEPES-buffered media (HCO 3 --free), the pH i recovery from acidification through NHE can be inhibited by removal of [Na + ] o or by the addition of a specific and potent NHE1 inhibitor, such as Hoe 694 [26,27]. However, in CO 2 /HCO 3 -buffered Tyrode solution, NBC coexists with NHE to achieve acid-equivalent extrusion in many mammalian cells [24,25,27,28]. This cotransporter of NBC is largely (56% to 91%) 4, 4-diisothiocyanatostilbene-2, 2-disulphonic acid (DIDS) sensitive, while HOE 694-resistant [23,25,[27][28][29].…”

“…However, in CO 2 /HCO 3 -buffered Tyrode solution, NBC coexists with NHE to achieve acid-equivalent extrusion in many mammalian cells [24,25,27,28]. This cotransporter of NBC is largely (56% to 91%) 4, 4-diisothiocyanatostilbene-2, 2-disulphonic acid (DIDS) sensitive, while HOE 694-resistant [23,25,[27][28][29]. NBC is also inhibited by removal of external Na + [29,30].…”

Functional diversity of electrogenic Na+–HCO3− cotransport in ventricular myocytes from rat, rabbit and guinea pig

“…Although NBC has been identified in cardiac tissue from guinea pig (Lagadic‐Gossmann et al 1992), sheep (Dart & Vaughan‐Jones, 1992), rat (Ng et al 1993; Kohout & Rogers, 1995; Le Prigent et al 1997; Aiello et al 1998; Khandoudi et al 2001), cat (Camilión de Hurtado et al 1995), ferret (Grace et al 1993; Vandenberg et al 1993) and human (Loh et al 2002), its existence in rabbit ventricle is unresolved. Rabbit NBC was thus evaluated in the first series of experiments.…”