Role of BK channels in hypertension and potassium secretion.

Purpose Of Review: This review summarizes recent studies of hypertension associated with a defect in renal K excretion due to genetic deletions of various components of the large, Ca-activated K channel (BK), and describes new evidence and theories regarding K secretory roles of BK in intercalated cells.

Recent Findings: Isolated perfused tubule methods have revealed the importance of BK in flow-induced K secretion. Subsequently, mice with genetically deleted BK subunits revealed the complexities of BK-mediated K secretion.

Coupled ATP and potassium efflux from intercalated cells.

Increased flow in the distal nephron induces K secretion through the large-conductance, calcium-activated K channel (BK), which is primarily expressed in intercalated cells (IC). Since flow also increases ATP release from IC, we hypothesized that purinergic signaling has a role in shear stress (τ; 10 dynes/cm(2)) -induced, BK-dependent, K efflux. We found that 10 μM ATP led to increased IC Ca concentration, which was significantly reduced in the presence of the P(2) receptor blocker suramin or calcium-free buffer.

Shear stress-induced volume decrease in C11-MDCK cells by BK-alpha/beta4.

Large-conductance, calcium-activated potassium channels (BK) are expressed in principal cells (PC) and intercalated cells (IC) in mammalian nephrons as BK-alpha/beta1 and BK-alpha/beta4, respectively. IC, which protrude into the lumens of tubules, express substantially more BK than PC despite lacking sufficient Na-K-ATPase to support K secretion. We previously showed in mice that IC exhibit size reduction when experiencing high distal flows induced by a high-K diet.

Intercalated cell BK-alpha/beta4 channels modulate sodium and potassium handling during potassium adaptation.

The large-conductance, calcium-activated potassium (BK) channels help eliminate potassium in mammals consuming potassium-rich diets. In the distal nephron, principal cells contain BK-alpha/beta1 channels and intercalated cells contain BK-alpha/beta4 channels. We studied whether BK-beta4-deficient mice (Kcnmb4(-/-)) have altered renal sodium and potassium clearances compared with wild-type mice when fed a regular or potassium-rich diet for ten days.

Hypertension of Kcnmb1-/- is linked to deficient K secretion and aldosteronism.

Mice lacking the beta1-subunit (gene, Kcnmb1; protein, BK-beta1) of the large Ca-activated K channel (BK) are hypertensive. This phenotype is thought to result from diminished BK currents in vascular smooth muscle where BK-beta1 is an ancillary subunit. However, the beta1-subunit is also expressed in the renal connecting tubule (CNT), a segment of the aldosterone-sensitive distal nephron, where it associates with BK and facilitates K secretion.

Role of BKbeta1 in Na+ reabsorption by cortical collecting ducts of Na+-deprived mice.

On a low-Na(+) diet (LNa(+)), urinary Na(+) loss is prevented by aldosterone-induced Na(+) reabsorption through epithelial Na(+) channels (ENaC) in the connecting tubules (CNT) and cortical collecting ducts (CCD). However, the mechanism whereby K(+) loss is minimized and Na(+) reabsorption is maximized in the face of a reduced lumen-to-bath Na(+) gradient is not fully understood. The large-conductance calcium-activated potassium channel (BK)beta1 subunit (gene: Kcnmb1), which has a role in K(+) secretion in the CNT, is absent in the CCD in mice on a control diet.

Incorporating a new bioinformatics component into genetics at a historically black college: outcomes and lessons.

Many students at minority-serving institutions are underexposed to Internet resources such as the human genome project, PubMed, NCBI databases, and other Web-based technologies because of a lack of financial resources. To change this, we designed and implemented a new bioinformatics component to supplement the undergraduate Genetics course at Clark Atlanta University. The outcomes of the Bioinformatics course were assessed.

Enhanced pulmonary and systemic response to endotoxin in transgenic sickle mice.

Some suggest that sickle cell disease (SCD) is associated with a "proinflammatory state" that predisposes patients to acute chest syndrome in the setting of triggering factors. Conflicting data emerged when inflammation markers in SCD were compared with healthy individuals. Therefore, we examined transgenic sickle and control mice at baseline and with endotoxin (LPS) intraperitoneal injection to determine whether a proinflammatory state truly exists.

Rehydration of high-density sickle erythrocytes in vitro.

Recent studies have identified older, low-density sickle red blood cells (SSRBCs) that were resistant to dehydration by valinomycin, a K(+) ionophore. These cells, thought to derive from dense SSRBCs that have rehydrated, may represent a terminal cellular phase. To study rehydration, we subjected dense SSRBCs (rho > 1.